rs1060504434

Positions:

• chr19-11026305-C-A
• chr19-11026305-C-G
• chr19-11026305-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003072.5(SMARCA4):​c.3174C>A​(p.Ser1058Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000684 in 1,461,582 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMARCA4 NM_003072.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.3174C>A	p.Ser1058Ser	synonymous_variant	23/36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.3174C>A	p.Ser1058Ser	synonymous_variant	23/35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.3174C>A	p.Ser1058Ser	synonymous_variant	23/36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.3174C>A	p.Ser1058Ser	synonymous_variant	23/35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.3174C>A	p.Ser1058Ser	synonymous_variant	23/35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.3174C>A	p.Ser1058Ser	synonymous_variant	24/35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.3174C>A	p.Ser1058Ser	synonymous_variant	23/34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.3174C>A	p.Ser1058Ser	synonymous_variant	23/34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.3174C>A	p.Ser1058Ser	synonymous_variant	24/35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.2586C>A	p.Ser862Ser	synonymous_variant	20/32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.1818C>A	p.Ser606Ser	synonymous_variant	16/28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.1899C>A	p.Ser633Ser	synonymous_variant	16/27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.1659C>A	p.Ser553Ser	synonymous_variant	15/27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.1527C>A	p.Ser509Ser	synonymous_variant	14/25			ENSP00000494159.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461582 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727102

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: 8.99e-7

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	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.60
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: chr19-11136981;