rs9891330

Positions:

• chr17-34157781-G-C

Variant summary

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

The ENST00000583224.3(ENSG00000263571):​n.1137+1079G>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 147,662 control chromosomes in the GnomAD database, including 10,718 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 0.38 (10718 hom., cov: 30)
• Consequence: ENST00000583224.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

Genes affected

(HGNC:):

ASIC2 (HGNC:99): (acid sensing ion channel subunit 2) This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, 2 hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene may play a role in neurotransmission. In addition, a heteromeric association between this member and acid-sensing (proton-gated) ion channel 3 has been observed to co-assemble into proton-gated channels sensitive to gadolinium. Alternative splicing has been observed at this locus and two variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000583224.3	n.1137+1079G>C		intron_variant, non_coding_transcript_variant		5
ASIC2	ENST00000583395.1	n.406-498C>G		intron_variant, non_coding_transcript_variant		2
	ENST00000667899.1	n.1089+1079G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.381 AC: 56193 AN: 147548 Hom.: 10711 Cov.: 30

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.381 AC: 56226 AN: 147662 Hom.: 10718 Cov.: 30 AF XY: 0.378 AC XY: 27296 AN XY: 72170

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.411

Alfa AF: 0.404 Hom.: 1188

Bravo AF: 0.383

Asia WGS AF: 0.252 AC: 788 AN: 3120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9891330; hg19: chr17-32484800;