rs4804556

chr19-10974867-T-Cchr19-10974867-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387283.1(SMARCA4):c.-28-9257T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 148,796 control chromosomes in the GnomAD database, including 9,139 homozygotes. 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: 𝑓 0.35 (9139 hom., cov: 24)
• Consequence: SMARCA4 NM_001387283.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA4	NM_001387283.1	c.-28-9257T>C		intron_variant		ENST00000646693.2
SMARCA4	NM_003072.5	c.-31-9254T>C		intron_variant		ENST00000344626.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA4	ENST00000344626.10	c.-31-9254T>C		intron_variant		1	NM_003072.5	P4
SMARCA4	ENST00000646693.2	c.-28-9257T>C		intron_variant			NM_001387283.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 51669 AN: 148698 Hom.: 9115 Cov.: 24

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.348 AC: 51737 AN: 148796 Hom.: 9139 Cov.: 24 AF XY: 0.346 AC XY: 25101 AN XY: 72536

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.343

Alfa AF: 0.331 Hom.: 1018

Bravo AF: 0.344

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	4.4
Dann	Benign	0.36

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: rs4804556; hg19: chr19-11085543; COSMIC: COSV60808941;