19-11030816-C-A

Position:

• chr19-11030816-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP7

The NM_003072.5(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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMARCA4 NM_003072.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP7: Synonymous conserved (PhyloP=1.41 with no splicing effect.

Transcripts

RefSeq

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

Ensembl

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	15
DANN	Benign	0.73
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8

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: chr19-11141492;