rs7860079

chr9-2106237-G-C

Variant summary

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

The NM_003070.5(SMARCA2):c.3292+2068G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,268 control chromosomes in the GnomAD database, including 56,325 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 0.86 (56325 hom., cov: 33)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCA2	NM_003070.5	c.3292+2068G>C		intron_variant		ENST00000349721.8
SMARCA2	NM_001289396.1	c.3292+2068G>C		intron_variant
SMARCA2	NM_001289397.2	c.3118+2068G>C		intron_variant
SMARCA2	NM_139045.4	c.3292+2068G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA2	ENST00000349721.8	c.3292+2068G>C		intron_variant		5	NM_003070.5	P2

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130374 AN: 152150 Hom.: 56280 Cov.: 33

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.857 AC: 130474 AN: 152268 Hom.: 56325 Cov.: 33 AF XY: 0.859 AC XY: 63932 AN XY: 74446

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.844

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.845

Alfa AF: 0.840 Hom.: 6799

Bravo AF: 0.861

Asia WGS AF: 0.818 AC: 2843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.7
Dann	Benign	0.77

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: rs7860079; hg19: chr9-2106237;