rs281875230

Variant names:

• chr19-11030816-C-A
• rs281875230
• NM_001387283.1:c.3469C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-11030816-C-A
• chr19-11030816-C-G
• chr19-11030816-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP6_Moderate BP7

The NM_001387283.1(SMARCA4):​c.3469C>A​(p.Arg1157Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R1157R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMARCA4 NM_001387283.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.41
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-11030816-C-A is Benign according to our data. Variant chr19-11030816-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3656649.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.41 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.3469C>A	p.Arg1157Arg	synonymous_variant	Exon 25 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.3469C>A	p.Arg1157Arg	synonymous_variant	Exon 25 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.3469C>A	p.Arg1157Arg	synonymous_variant	Exon 25 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.3469C>A	p.Arg1157Arg	synonymous_variant	Exon 25 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.3469C>A	p.Arg1157Arg	synonymous_variant	Exon 25 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.3469C>A	p.Arg1157Arg	synonymous_variant	Exon 26 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.3469C>A	p.Arg1157Arg	synonymous_variant	Exon 25 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.3469C>A	p.Arg1157Arg	synonymous_variant	Exon 25 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.3469C>A	p.Arg1157Arg	synonymous_variant	Exon 26 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.2881C>A	p.Arg961Arg	synonymous_variant	Exon 22 of 32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.2113C>A	p.Arg705Arg	synonymous_variant	Exon 18 of 28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.2194C>A	p.Arg732Arg	synonymous_variant	Exon 18 of 27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.1954C>A	p.Arg652Arg	synonymous_variant	Exon 17 of 27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.1822C>A	p.Arg608Arg	synonymous_variant	Exon 16 of 25			ENSP00000494159.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455952 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723748

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.00 AC: 0 AN: 85084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109564

Other (OTH) AF: 0.00 AC: 0 AN: 60164

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Benign:1

Jun 14, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	15
DANN	Benign	0.73
PhyloP100		1.4
PromoterAI		0.0028	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8
Mutation Taster		=66/34	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: rs281875230; hg19: chr19-11141492;