rs3786721

Positions:

• chr19-11035823-T-C

Variant summary

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

The ENST00000344626.10(SMARCA4):​c.4170+691T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,216 control chromosomes in the GnomAD database, including 26,496 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 0.59 (26496 hom., cov: 34)
• Consequence: SMARCA4 ENST00000344626.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.4170+691T>C		intron_variant		ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.4170+691T>C		intron_variant		ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000344626.10	c.4170+691T>C		intron_variant		1	NM_003072.5	ENSP00000343896	P4
SMARCA4	ENST00000646693.2	c.4170+691T>C		intron_variant			NM_001387283.1	ENSP00000495368

Frequencies

GnomAD3 genomes AF: 0.585 AC: 89041 AN: 152098 Hom.: 26438 Cov.: 34

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.586 AC: 89159 AN: 152216 Hom.: 26496 Cov.: 34 AF XY: 0.587 AC XY: 43652 AN XY: 74426

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.578

Alfa AF: 0.556 Hom.: 34108

Bravo AF: 0.588

Asia WGS AF: 0.697 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.55

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: rs3786721; hg19: chr19-11146499;