NM_003070.5:c.3981+6980G>A

Variant names:

• chr9-2130917-G-A
• rs6475522
• NM_003070.5:c.3981+6980G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.3981+6980G>A		intron_variant	Intron 27 of 33	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.2	c.3981+6980G>A		intron_variant	Intron 27 of 33		NP_001276325.1
SMARCA2	NM_139045.4	c.3981+6980G>A		intron_variant	Intron 27 of 32		NP_620614.2
SMARCA2	NM_001289397.2	c.3807+6980G>A		intron_variant	Intron 27 of 32		NP_001276326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8	c.3981+6980G>A		intron_variant	Intron 27 of 33	5	NM_003070.5	ENSP00000265773.5

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

African (AFR) AF: 0.295 AC: 12235 AN: 41442

American (AMR) AF: 0.146 AC: 2229 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3470

East Asian (EAS) AF: 0.436 AC: 2253 AN: 5168

South Asian (SAS) AF: 0.213 AC: 1025 AN: 4818

European-Finnish (FIN) AF: 0.0883 AC: 936 AN: 10598

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0988 AC: 6718 AN: 67998

Other (OTH) AF: 0.157 AC: 331 AN: 2112

Alfa AF: 0.0986 Hom.: 448

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
PhyloP100		-2.7
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: rs6475522; hg19: chr9-2130917;