rs11879293

Positions:

• chr19-10961934-G-A
• chr19-10961934-G-C
• chr19-10961934-G-T

Variant summary

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

The NM_001387283.1(SMARCA4):​c.-29+760G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 150,490 control chromosomes in the GnomAD database, including 10,295 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 0.37 (10295 hom., cov: 29)
• Consequence: SMARCA4 NM_001387283.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.-29+760G>A		intron_variant		ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.-32+760G>A		intron_variant		ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000344626.10	c.-32+760G>A		intron_variant		1	NM_003072.5	ENSP00000343896	P4
SMARCA4	ENST00000646693.2	c.-29+760G>A		intron_variant			NM_001387283.1	ENSP00000495368

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55428 AN: 150400 Hom.: 10279 Cov.: 29

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.369 AC: 55490 AN: 150490 Hom.: 10295 Cov.: 29 AF XY: 0.367 AC XY: 26947 AN XY: 73332

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.369

Alfa AF: 0.387 Hom.: 6776

Bravo AF: 0.364

Asia WGS AF: 0.392 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11879293; hg19: chr19-11072610;