17-33482508-G-A

Variant names:

• chr17-33482508-G-A
• rs12453548
• ENST00000359872.6:c.556-370441C>T

Variant summary

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

The NM_001094.5(ASIC2):​c.556-370441C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,108 control chromosomes in the GnomAD database, including 3,852 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 0.20 (3852 hom., cov: 33)
• Consequence: ASIC2 NM_001094.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 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.556-370441C>T		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.556-370441C>T		intron	N/A	ENSP00000352934.6	Q16515-1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30965 AN: 151990 Hom.: 3850 Cov.: 33

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.204 AC: 30973 AN: 152108 Hom.: 3852 Cov.: 33 AF XY: 0.203 AC XY: 15128 AN XY: 74350

African (AFR) AF: 0.0575 AC: 2389 AN: 41516

American (AMR) AF: 0.244 AC: 3732 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3470

East Asian (EAS) AF: 0.0908 AC: 469 AN: 5166

South Asian (SAS) AF: 0.213 AC: 1029 AN: 4820

European-Finnish (FIN) AF: 0.264 AC: 2789 AN: 10558

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18831 AN: 67978

Other (OTH) AF: 0.207 AC: 437 AN: 2110

Alfa AF: 0.244 Hom.: 8289

Bravo AF: 0.195

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.73
PhyloP100		0.51
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: rs12453548; hg19: chr17-31809526;