rs878854205

Variant names:

• chr19-11010539-AGG-A
• rs878854205
• NM_001387283.1:c.2274+12_2274+13delGG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_001387283.1(SMARCA4):​c.2274+12_2274+13delGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,612,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: SMARCA4 NM_001387283.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.106
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 19-11010539-AGG-A is Benign according to our data. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11010539-AGG-A is described in CliVar as Likely_benign. Clinvar id is 238396.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000658 (10/152012) while in subpopulation NFE AF = 0.000147 (10/67958). AF 95% confidence interval is 0.0000792. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.2274+12_2274+13delGG		intron_variant	Intron 15 of 35	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.2274+12_2274+13delGG		intron_variant	Intron 15 of 34	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.2274+9_2274+10delGG		intron_variant	Intron 15 of 35		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.2274+9_2274+10delGG		intron_variant	Intron 15 of 34	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.2274+9_2274+10delGG		intron_variant	Intron 15 of 34			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.2274+9_2274+10delGG		intron_variant	Intron 16 of 34	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.2274+9_2274+10delGG		intron_variant	Intron 15 of 33			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.2274+9_2274+10delGG		intron_variant	Intron 15 of 33			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.2274+9_2274+10delGG		intron_variant	Intron 16 of 34	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.1686+9_1686+10delGG		intron_variant	Intron 12 of 31			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.918+9_918+10delGG		intron_variant	Intron 8 of 27			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.999+9_999+10delGG		intron_variant	Intron 8 of 26			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.759+9_759+10delGG		intron_variant	Intron 7 of 26			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.627+9_627+10delGG		intron_variant	Intron 6 of 24			ENSP00000494159.1

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152012 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000124 AC: 31 AN: 250434 AF XY: 0.000133

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000171 AC: 250 AN: 1460912 Hom.: 0 AF XY: 0.000165 AC XY: 120 AN XY: 726778

African (AFR) AF: 0.0000896 AC: 3 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000215 AC: 239 AN: 1111876

Other (OTH) AF: 0.000132 AC: 8 AN: 60386

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 152012 Hom.: 0 Cov.: 31 AF XY: 0.0000808 AC XY: 6 AN XY: 74250

African (AFR) AF: 0.00 AC: 0 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000217 Hom.: 0

Bravo AF: 0.0000718

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs878854205; hg19: chr19-11121215;