rs11669133

Positions:

• chr19-10981463-G-A

Variant summary

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

The NM_001387283.1(SMARCA4):​c.-28-2661G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 152,332 control chromosomes in the GnomAD database, including 168 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 0.041 (168 hom., cov: 32)
• Consequence: SMARCA4 NM_001387283.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.965

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA4	NM_001387283.1	c.-28-2661G>A		intron_variant		ENST00000646693.2
SMARCA4	NM_003072.5	c.-31-2658G>A		intron_variant		ENST00000344626.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA4	ENST00000344626.10	c.-31-2658G>A		intron_variant		1	NM_003072.5	P4
SMARCA4	ENST00000646693.2	c.-28-2661G>A		intron_variant			NM_001387283.1

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6194 AN: 152214 Hom.: 167 Cov.: 32

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0294

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0212

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0449

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

GnomAD4 genome AF: 0.0407 AC: 6206 AN: 152332 Hom.: 168 Cov.: 32 AF XY: 0.0380 AC XY: 2832 AN XY: 74484

Gnomad4 AFR AF: 0.0597

Gnomad4 AMR AF: 0.0294

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0212

Gnomad4 NFE AF: 0.0414

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0386 Hom.: 143

Bravo AF: 0.0423

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.57

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: rs11669133; hg19: chr19-11092139;