chr19-11052886-C-T

Position:

• chr19-11052886-C-T

Variant summary

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

The ENST00000344626.10(SMARCA4):​c.4425-5369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,020 control chromosomes in the GnomAD database, including 26,279 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 0.58 (26279 hom., cov: 31)
• Consequence: SMARCA4 ENST00000344626.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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 (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.4521-5369C>T		intron_variant		ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.4425-5369C>T		intron_variant		ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000344626.10	c.4425-5369C>T		intron_variant		1	NM_003072.5	ENSP00000343896	P4
SMARCA4	ENST00000646693.2	c.4521-5369C>T		intron_variant			NM_001387283.1	ENSP00000495368

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88406 AN: 151902 Hom.: 26250 Cov.: 31

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.582 AC: 88483 AN: 152020 Hom.: 26279 Cov.: 31 AF XY: 0.578 AC XY: 42967 AN XY: 74304

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.550

Alfa AF: 0.540 Hom.: 47500

Bravo AF: 0.586

Asia WGS AF: 0.589 AC: 2048 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	0.34
DANN	Benign	0.28

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: rs1529729; hg19: chr19-11163562;