17-33622760-C-T

Variant names:

• chr17-33622760-C-T
• rs1560916
• ENST00000359872.6:c.556-510693G>A

Variant summary

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

The NM_001094.5(ASIC2):​c.556-510693G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,048 control chromosomes in the GnomAD database, including 21,377 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 0.52 (21377 hom., cov: 33)
• Consequence: ASIC2 NM_001094.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428
• 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]

ENSG00000265125 (HGNC:27103):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

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.556-510693G>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.556-510693G>A		intron	N/A	ENSP00000352934.6	Q16515-1
	ENSG00000265125	ENST00000579975.1	TSL:3	n.509-694C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79372 AN: 151928 Hom.: 21345 Cov.: 33

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.522 AC: 79442 AN: 152048 Hom.: 21377 Cov.: 33 AF XY: 0.512 AC XY: 38032 AN XY: 74286

African (AFR) AF: 0.636 AC: 26368 AN: 41484

American (AMR) AF: 0.415 AC: 6348 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3472

East Asian (EAS) AF: 0.495 AC: 2554 AN: 5156

South Asian (SAS) AF: 0.435 AC: 2100 AN: 4826

European-Finnish (FIN) AF: 0.362 AC: 3822 AN: 10546

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34854 AN: 67960

Other (OTH) AF: 0.508 AC: 1075 AN: 2116

Alfa AF: 0.517 Hom.: 61542

Bravo AF: 0.531

Asia WGS AF: 0.439 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.2
DANN	Benign	0.79
PhyloP100		0.43
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: rs1560916; hg19: chr17-31949779;