9-2177492-A-G

Variant names:

• chr9-2177492-A-G
• rs10491697
• NM_003070.5:c.4254-4079A>G

Variant summary

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

The NM_003070.5(SMARCA2):​c.4254-4079A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,958 control chromosomes in the GnomAD database, including 7,614 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 0.29 (7614 hom., cov: 32)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.888

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.4254-4079A>G		intron_variant	Intron 29 of 33	ENST00000349721.8	NP_003061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8	c.4254-4079A>G		intron_variant	Intron 29 of 33	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43894 AN: 151840 Hom.: 7598 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.289 AC: 43959 AN: 151958 Hom.: 7614 Cov.: 32 AF XY: 0.291 AC XY: 21608 AN XY: 74274

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.291

Alfa AF: 0.209 Hom.: 4970

Bravo AF: 0.311

Asia WGS AF: 0.351 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
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: rs10491697; hg19: chr9-2177492; COSMIC: COSV56648605; COSMIC: COSV56648605;