rs7048976

Variant names:

• chr9-2173296-G-T
• rs7048976
• NM_003070.5:c.4253+2824G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

SMARCA2 Gene-Disease associations (from GenCC):

• intellectual disability-sparse hair-brachydactyly syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000306181 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.4253+2824G>T		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.4253+2824G>T		intron_variant	Intron 29 of 33	5	NM_003070.5	ENSP00000265773.5

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

African (AFR) AF: 0.423 AC: 17525 AN: 41428

American (AMR) AF: 0.641 AC: 9791 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1646 AN: 3466

East Asian (EAS) AF: 0.671 AC: 3463 AN: 5162

South Asian (SAS) AF: 0.550 AC: 2652 AN: 4820

European-Finnish (FIN) AF: 0.584 AC: 6180 AN: 10574

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35474 AN: 67956

Other (OTH) AF: 0.530 AC: 1120 AN: 2112

Alfa AF: 0.518 Hom.: 34690

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
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7048976; hg19: chr9-2173296;