rs7048976

Positions:

• chr9-2173296-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.4253+2824G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,000 control chromosomes in the GnomAD database, including 20,765 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 0.52 (20765 hom., cov: 32)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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]

LOC107987043 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.4253+2824G>T		intron_variant		ENST00000349721.8
LOC107987043	XR_007061395.1	n.3688-1068C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.4253+2824G>T		intron_variant		5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78476 AN: 151882 Hom.: 20750 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.517 AC: 78530 AN: 152000 Hom.: 20765 Cov.: 32 AF XY: 0.527 AC XY: 39150 AN XY: 74314

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.530

Alfa AF: 0.519 Hom.: 27535

Bravo AF: 0.520

Asia WGS AF: 0.626 AC: 2174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.74

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: rs7048976; hg19: chr9-2173296;