rs117364231

Variant names:

• chr17-33979404-C-T
• rs117364231
• ENST00000359872.6:c.555+176574G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001094.5(ASIC2):​c.555+176574G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 152,244 control chromosomes in the GnomAD database, including 40 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 0.018 (40 hom., cov: 32)
• Consequence: ASIC2 NM_001094.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• 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=-0.91).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0176 (2681/152244) while in subpopulation EAS AF = 0.0518 (268/5172). AF 95% confidence interval is 0.0467. There are 40 homozygotes in GnomAd4. There are 1276 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2681 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001094.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	NM_001094.5		c.555+176574G>A		intron	N/A	NP_001085.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000359872.6	TSL:1	c.555+176574G>A		intron	N/A	ENSP00000352934.6	Q16515-1
	ENSG00000263435	ENST00000582685.1	TSL:3	n.217-1341C>T		intron	N/A
	ENSG00000279668	ENST00000584758.2	TSL:5	n.188+4783G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2683 AN: 152126 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.00367

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.00989

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0176 AC: 2681 AN: 152244 Hom.: 40 Cov.: 32 AF XY: 0.0171 AC XY: 1276 AN XY: 74452

African (AFR) AF: 0.00366 AC: 152 AN: 41528

American (AMR) AF: 0.0162 AC: 247 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3472

East Asian (EAS) AF: 0.0518 AC: 268 AN: 5172

South Asian (SAS) AF: 0.0240 AC: 116 AN: 4824

European-Finnish (FIN) AF: 0.00989 AC: 105 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0243 AC: 1650 AN: 68022

Other (OTH) AF: 0.0189 AC: 40 AN: 2112

Alfa AF: 0.0229 Hom.: 66

Bravo AF: 0.0175

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.45
PhyloP100		-0.023
Mutation Taster		=100/0	polymorphism

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: rs117364231; hg19: chr17-32306423;