chr9-2127796-G-A

Variant names:

• chr9-2127796-G-A
• rs3829072
• NM_003070.5:c.3981+3859G>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+3859G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,078 control chromosomes in the GnomAD database, including 12,061 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 0.31 (12061 hom., cov: 32)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.3981+3859G>A		intron_variant	Intron 27 of 33	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.2	c.3981+3859G>A		intron_variant	Intron 27 of 33		NP_001276325.1
SMARCA2	NM_139045.4	c.3981+3859G>A		intron_variant	Intron 27 of 32		NP_620614.2
SMARCA2	NM_001289397.2	c.3807+3859G>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+3859G>A		intron_variant	Intron 27 of 33	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46584 AN: 151960 Hom.: 12011 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.307 AC: 46693 AN: 152078 Hom.: 12061 Cov.: 32 AF XY: 0.307 AC XY: 22804 AN XY: 74348

African (AFR) AF: 0.701 AC: 29076 AN: 41458

American (AMR) AF: 0.198 AC: 3026 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3468

East Asian (EAS) AF: 0.437 AC: 2257 AN: 5168

South Asian (SAS) AF: 0.214 AC: 1030 AN: 4814

European-Finnish (FIN) AF: 0.171 AC: 1804 AN: 10576

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8456 AN: 67986

Other (OTH) AF: 0.249 AC: 525 AN: 2112

Alfa AF: 0.175 Hom.: 17079

Bravo AF: 0.327

Asia WGS AF: 0.325 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.59
PhyloP100		0.19
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: rs3829072; hg19: chr9-2127796; COSMIC: COSV61805770;