NM_001387283.1:c.4788C>T

Variant names:

• chr19-11059809-C-T
• rs746415437
• NM_001387283.1:c.4788C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_001387283.1(SMARCA4):​c.4788C>T​(p.Ile1596Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,611,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: SMARCA4 NM_001387283.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -4.27
• Publications: 0 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 19-11059809-C-T is Benign according to our data. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11059809-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.27 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000138 (21/152166) while in subpopulation AMR AF = 0.00105 (16/15270). AF 95% confidence interval is 0.000657. There are 0 homozygotes in GnomAd4. There are 12 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.4788C>T	p.Ile1596Ile	synonymous_variant	Exon 34 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.4692C>T	p.Ile1564Ile	synonymous_variant	Exon 33 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.4788C>T	p.Ile1596Ile	synonymous_variant	Exon 34 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.4692C>T	p.Ile1564Ile	synonymous_variant	Exon 33 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.4698C>T	p.Ile1566Ile	synonymous_variant	Exon 33 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.4602C>T	p.Ile1534Ile	synonymous_variant	Exon 33 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.4602C>T	p.Ile1534Ile	synonymous_variant	Exon 32 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.4602C>T	p.Ile1534Ile	synonymous_variant	Exon 32 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.4599C>T	p.Ile1533Ile	synonymous_variant	Exon 33 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.4113C>T	p.Ile1371Ile	synonymous_variant	Exon 30 of 32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.3342C>T	p.Ile1114Ile	synonymous_variant	Exon 26 of 28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.3324C>T	p.Ile1108Ile	synonymous_variant	Exon 25 of 27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.3186C>T	p.Ile1062Ile	synonymous_variant	Exon 25 of 27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.2952C>T	p.Ile984Ile	synonymous_variant	Exon 23 of 25			ENSP00000494159.1
SMARCA4	ENST00000538456.4	c.756C>T	p.Ile252Ile	synonymous_variant	Exon 6 of 8	3		ENSP00000495197.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000660 AC: 16 AN: 242466 AF XY: 0.0000836

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000472

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000281 AC: 41 AN: 1459032 Hom.: 0 Cov.: 32 AF XY: 0.0000303 AC XY: 22 AN XY: 725652

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.000452 AC: 20 AN: 44234

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1110672

Other (OTH) AF: 0.0000830 AC: 5 AN: 60256

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152166 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74338

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.00105 AC: 16 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.000106

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Aug 03, 2022

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SMARCA4: BP4, BP7 -

Mar 19, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:2

Mar 19, 2021

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Jul 01, 2015

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. -

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

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.17
DANN	Benign	0.57
PhyloP100		-4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs746415437; hg19: chr19-11170485; COSMIC: COSV60804330; COSMIC: COSV60804330;