rs1555785323

Positions:

• chr19-11034916-C-G
• chr19-11034916-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.3954C>G​(p.Arg1318Arg) variant causes a splice region, 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

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=-0.26).
• BP7: Synonymous conserved (PhyloP=0.388 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.3954C>G	p.Arg1318Arg	splice_region_variant, synonymous_variant	29/36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.3954C>G	p.Arg1318Arg	splice_region_variant, synonymous_variant	29/35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.3954C>G	p.Arg1318Arg	splice_region_variant, synonymous_variant	29/36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.3954C>G	p.Arg1318Arg	splice_region_variant, synonymous_variant	29/35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.3855C>G	p.Arg1285Arg	splice_region_variant, synonymous_variant	28/35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.3855C>G	p.Arg1285Arg	splice_region_variant, synonymous_variant	29/35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.3855C>G	p.Arg1285Arg	splice_region_variant, synonymous_variant	28/34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.3855C>G	p.Arg1285Arg	splice_region_variant, synonymous_variant	28/34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.3855C>G	p.Arg1285Arg	splice_region_variant, synonymous_variant	29/35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.3366C>G	p.Arg1122Arg	splice_region_variant, synonymous_variant	26/32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.2598C>G	p.Arg866Arg	splice_region_variant, synonymous_variant	22/28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.2580C>G	p.Arg860Arg	splice_region_variant, synonymous_variant	21/27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.2439C>G	p.Arg813Arg	splice_region_variant, synonymous_variant	21/27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.2307C>G	p.Arg769Arg	splice_region_variant, synonymous_variant	20/25			ENSP00000494159.1
SMARCA4	ENST00000538456.4	c.111C>G	p.Arg37Arg	splice_region_variant, synonymous_variant	3/8	3		ENSP00000495197.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.86
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-11145592;