rs750609318

Variant names:

• chr19-11023541-C-G
• rs750609318
• NM_001387283.1:c.2883C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-11023541-C-G
• chr19-11023541-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003072.5(SMARCA4):​c.2883C>G​(p.Thr961Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMARCA4 NM_003072.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=-1.59 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.2883C>G	p.Thr961Thr	synonymous_variant	Exon 20 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.2883C>G	p.Thr961Thr	synonymous_variant	Exon 20 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.2883C>G	p.Thr961Thr	synonymous_variant	Exon 20 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.2883C>G	p.Thr961Thr	synonymous_variant	Exon 20 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.2883C>G	p.Thr961Thr	synonymous_variant	Exon 20 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.2883C>G	p.Thr961Thr	synonymous_variant	Exon 21 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.2883C>G	p.Thr961Thr	synonymous_variant	Exon 20 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.2883C>G	p.Thr961Thr	synonymous_variant	Exon 20 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.2883C>G	p.Thr961Thr	synonymous_variant	Exon 21 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.2295C>G	p.Thr765Thr	synonymous_variant	Exon 17 of 32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.1527C>G	p.Thr509Thr	synonymous_variant	Exon 13 of 28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.1608C>G	p.Thr536Thr	synonymous_variant	Exon 13 of 27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.1368C>G	p.Thr456Thr	synonymous_variant	Exon 12 of 27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.1236C>G	p.Thr412Thr	synonymous_variant	Exon 11 of 25			ENSP00000494159.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.5
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs750609318; hg19: chr19-11134217;