rs55791371

chr19-11077477-A-Cchr19-11077477-A-T

Variant summary

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

The ENST00000645236.1(SMARCA4):c.1458-1520A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,116 control chromosomes in the GnomAD database, including 966 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 0.11 (966 hom., cov: 31)
• Consequence: SMARCA4 ENST00000645236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA4	ENST00000645236.1	c.1458-1520A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16305 AN: 151998 Hom.: 967 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0939

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00807

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.107 AC: 16307 AN: 152116 Hom.: 966 Cov.: 31 AF XY: 0.107 AC XY: 7946 AN XY: 74350

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0937

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.00809

Gnomad4 SAS AF: 0.0679

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.108

Alfa AF: 0.101 Hom.: 364

Bravo AF: 0.109

Asia WGS AF: 0.0530 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.4
Dann	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs55791371; hg19: chr19-11188153;