rs317331

Variant names:

• chr17-33979233-C-T
• rs317331
• ENST00000359872.6:c.555+176745G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359872.6(ASIC2):​c.555+176745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,102 control chromosomes in the GnomAD database, including 2,359 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 0.16 (2359 hom., cov: 32)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 2 publications found

Genes affected

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]

ENSG00000263435 (HGNC:58620):

ENSG00000279668 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_001094.5	c.555+176745G>A		intron_variant	Intron 1 of 9		NP_001085.2
LOC107985038	XR_001752840.2	n.221+7912G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000359872.6	c.555+176745G>A		intron_variant	Intron 1 of 9	1		ENSP00000352934.6
ENSG00000263435	ENST00000582685.1	n.217-1512C>T		intron_variant	Intron 1 of 1	3
ENSG00000279668	ENST00000584758.2	n.188+4954G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23687 AN: 151984 Hom.: 2359 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.156 AC: 23691 AN: 152102 Hom.: 2359 Cov.: 32 AF XY: 0.153 AC XY: 11366 AN XY: 74338

African (AFR) AF: 0.0442 AC: 1833 AN: 41506

American (AMR) AF: 0.197 AC: 3004 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3470

East Asian (EAS) AF: 0.102 AC: 528 AN: 5158

South Asian (SAS) AF: 0.132 AC: 634 AN: 4818

European-Finnish (FIN) AF: 0.170 AC: 1804 AN: 10594

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14924 AN: 67972

Other (OTH) AF: 0.138 AC: 290 AN: 2108

Alfa AF: 0.200 Hom.: 5554

Bravo AF: 0.152

Asia WGS AF: 0.123 AC: 431 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.059
DANN	Benign	0.66
PhyloP100		-1.8
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: rs317331; hg19: chr17-32306252;