rs1467214059

Variant names:

• chr19-11034970-C-A
• NM_001387283.1:c.4008C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-11034970-C-A
• chr19-11034970-C-G
• chr19-11034970-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_003072.5(SMARCA4):​c.4008C>A​(p.Arg1336Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMARCA4 NM_003072.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 19-11034970-C-A is Benign according to our data. Variant chr19-11034970-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2587145.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.4008C>A	p.Arg1336Arg	synonymous_variant	Exon 29 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.4008C>A	p.Arg1336Arg	synonymous_variant	Exon 29 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.4008C>A	p.Arg1336Arg	synonymous_variant	Exon 29 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.4008C>A	p.Arg1336Arg	synonymous_variant	Exon 29 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.3909C>A	p.Arg1303Arg	synonymous_variant	Exon 28 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.3909C>A	p.Arg1303Arg	synonymous_variant	Exon 29 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.3909C>A	p.Arg1303Arg	synonymous_variant	Exon 28 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.3909C>A	p.Arg1303Arg	synonymous_variant	Exon 28 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.3909C>A	p.Arg1303Arg	synonymous_variant	Exon 29 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.3420C>A	p.Arg1140Arg	synonymous_variant	Exon 26 of 32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.2652C>A	p.Arg884Arg	synonymous_variant	Exon 22 of 28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.2634C>A	p.Arg878Arg	synonymous_variant	Exon 21 of 27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.2493C>A	p.Arg831Arg	synonymous_variant	Exon 21 of 27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.2361C>A	p.Arg787Arg	synonymous_variant	Exon 20 of 25			ENSP00000494159.1
SMARCA4	ENST00000538456.4	c.165C>A	p.Arg55Arg	synonymous_variant	Exon 3 of 8	3		ENSP00000495197.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1

Aug 24, 2023

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	5.8
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-11145646;