19-11024402-C-T

Variant names:

• chr19-11024402-C-T
• rs56101423
• NM_001387283.1:c.3045C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001387283.1(SMARCA4):​c.3045C>T​(p.Gly1015Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,612,958 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (5 hom.)
• Consequence: SMARCA4 NM_001387283.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:16
• Conservation: PhyloP100: -4.87
• Publications: 5 publications found

Genes affected

SMARCA4 (HGNC:11100): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

SMARCA4 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Illumina
• intellectual disability, autosomal dominant 16

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• rhabdoid tumor predisposition syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• uterine corpus sarcoma

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• familial rhabdoid tumor

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 19-11024402-C-T is Benign according to our data. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11024402-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 212248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.87 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00154 (235/152310) while in subpopulation NFE AF = 0.00256 (174/68020). AF 95% confidence interval is 0.00225. There are 0 homozygotes in GnomAd4. There are 120 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.3045C>T	p.Gly1015Gly	synonymous_variant	Exon 21 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.3045C>T	p.Gly1015Gly	synonymous_variant	Exon 21 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.3045C>T	p.Gly1015Gly	synonymous_variant	Exon 21 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.3045C>T	p.Gly1015Gly	synonymous_variant	Exon 21 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.3045C>T	p.Gly1015Gly	synonymous_variant	Exon 21 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.3045C>T	p.Gly1015Gly	synonymous_variant	Exon 22 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.3045C>T	p.Gly1015Gly	synonymous_variant	Exon 21 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.3045C>T	p.Gly1015Gly	synonymous_variant	Exon 21 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.3045C>T	p.Gly1015Gly	synonymous_variant	Exon 22 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.2457C>T	p.Gly819Gly	synonymous_variant	Exon 18 of 32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.1689C>T	p.Gly563Gly	synonymous_variant	Exon 14 of 28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.1770C>T	p.Gly590Gly	synonymous_variant	Exon 14 of 27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.1530C>T	p.Gly510Gly	synonymous_variant	Exon 13 of 27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.1398C>T	p.Gly466Gly	synonymous_variant	Exon 12 of 25			ENSP00000494159.1

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 235 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00146 AC: 365 AN: 250350 AF XY: 0.00139

Gnomad AFR exome AF: 0.000618

Gnomad AMR exome AF: 0.000811

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000792

Gnomad NFE exome AF: 0.00265

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00203 AC: 2963 AN: 1460648 Hom.: 5 Cov.: 31 AF XY: 0.00202 AC XY: 1466 AN XY: 726636

African (AFR) AF: 0.000329 AC: 11 AN: 33472

American (AMR) AF: 0.000894 AC: 40 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86252

European-Finnish (FIN) AF: 0.000628 AC: 33 AN: 52568

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.00248 AC: 2754 AN: 1111652

Other (OTH) AF: 0.00184 AC: 111 AN: 60380

GnomAD4 genome AF: 0.00154 AC: 235 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.00161 AC XY: 120 AN XY: 74474

African (AFR) AF: 0.000626 AC: 26 AN: 41556

American (AMR) AF: 0.00183 AC: 28 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00256 AC: 174 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00215 Hom.: 1

Bravo AF: 0.00158

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:16

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:8

Sep 29, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26327206) -

May 21, 2021

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SMARCA4: BP4, BP7, BS1 -

Nov 03, 2021

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hereditary cancer-predisposing syndrome Benign:2

Mar 30, 2017

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Aug 17, 2020

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

not specified Benign:1

Apr 25, 2016

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Intellectual disability, autosomal dominant 16 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Rhabdoid tumor predisposition syndrome 2 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Rhabdoid tumor predisposition syndrome 2;C3553249:Intellectual disability, autosomal dominant 16;C5935610:Otosclerosis 12 Benign:1

May 19, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Coffin-Siris syndrome Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

SMARCA4-related disorder Benign:1

Mar 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.0
DANN	Benign	0.72
PhyloP100		-4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56101423; hg19: chr19-11135078; COSMIC: COSV100758340; COSMIC: COSV100758340;