chr19-11017920-A-G

Position:

• chr19-11017920-A-G

Variant summary

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

The ENST00000344626.10(SMARCA4):​c.2439-1037A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,828 control chromosomes in the GnomAD database, including 12,929 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 0.41 (12929 hom., cov: 33)
• Consequence: SMARCA4 ENST00000344626.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.2439-1037A>G		intron_variant		ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.2439-1037A>G		intron_variant		ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000344626.10	c.2439-1037A>G		intron_variant		1	NM_003072.5	ENSP00000343896	P4
SMARCA4	ENST00000646693.2	c.2439-1037A>G		intron_variant			NM_001387283.1	ENSP00000495368

Frequencies

GnomAD3 genomes AF: 0.409 AC: 61990 AN: 151710 Hom.: 12883 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.409 AC: 62097 AN: 151828 Hom.: 12929 Cov.: 33 AF XY: 0.414 AC XY: 30714 AN XY: 74220

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.412

Alfa AF: 0.402 Hom.: 5637

Bravo AF: 0.402

Asia WGS AF: 0.526 AC: 1828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.87
DANN	Benign	0.14

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: rs11085754; hg19: chr19-11128596;