rs10964501

Positions:

• chr9-2034553-T-A
• chr9-2034553-T-G

Variant summary

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

The NM_003070.5(SMARCA2):​c.355+1472T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,068 control chromosomes in the GnomAD database, including 20,998 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 0.46 (20998 hom., cov: 32)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

Genes affected

SMARCA2 (HGNC:11098): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is highly 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, which contains a trinucleotide repeat (CAG) length polymorphism. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.355+1472T>A		intron_variant		ENST00000349721.8
SMARCA2	NM_001289396.1	c.355+1472T>A		intron_variant
SMARCA2	NM_001289397.2	c.355+1472T>A		intron_variant
SMARCA2	NM_139045.4	c.355+1472T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.355+1472T>A		intron_variant		5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70135 AN: 151950 Hom.: 20924 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.462 AC: 70273 AN: 152068 Hom.: 20998 Cov.: 32 AF XY: 0.462 AC XY: 34321 AN XY: 74348

Gnomad4 AFR AF: 0.853

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.407

Alfa AF: 0.403 Hom.: 1981

Bravo AF: 0.485

Asia WGS AF: 0.434 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.44
DANN	Benign	0.52

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: rs10964501; hg19: chr9-2034553;