rs6475522

Positions:

• chr9-2130917-G-A
• chr9-2130917-G-C
• chr9-2130917-G-T

Variant summary

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

The NM_003070.5(SMARCA2):​c.3981+6980G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,092 control chromosomes in the GnomAD database, including 3,066 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 0.17 (3066 hom., cov: 32)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.3981+6980G>A		intron_variant		ENST00000349721.8
SMARCA2	NM_001289396.1	c.3981+6980G>A		intron_variant
SMARCA2	NM_001289397.2	c.3807+6980G>A		intron_variant
SMARCA2	NM_139045.4	c.3981+6980G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.3981+6980G>A		intron_variant		5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26135 AN: 151976 Hom.: 3063 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0988

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.172 AC: 26174 AN: 152092 Hom.: 3066 Cov.: 32 AF XY: 0.174 AC XY: 12907 AN XY: 74384

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.0883

Gnomad4 NFE AF: 0.0988

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0886 Hom.: 211

Bravo AF: 0.182

Asia WGS AF: 0.287 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.053
DANN	Benign	0.47

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: rs6475522; hg19: chr9-2130917;