rs439783

Variant names:

• chr17-33350142-T-C
• rs439783
• ENST00000359872.6:c.556-238075A>G

Variant summary

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

The NM_001094.5(ASIC2):​c.556-238075A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,930 control chromosomes in the GnomAD database, including 18,754 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 0.48 (18754 hom., cov: 32)
• Consequence: ASIC2 NM_001094.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.634 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.556-238075A>G		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.556-238075A>G		intron	N/A	ENSP00000352934.6

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73484 AN: 151812 Hom.: 18719 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.484 AC: 73570 AN: 151930 Hom.: 18754 Cov.: 32 AF XY: 0.486 AC XY: 36091 AN XY: 74250

African (AFR) AF: 0.640 AC: 26519 AN: 41420

American (AMR) AF: 0.450 AC: 6868 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1373 AN: 3470

East Asian (EAS) AF: 0.636 AC: 3271 AN: 5146

South Asian (SAS) AF: 0.536 AC: 2579 AN: 4810

European-Finnish (FIN) AF: 0.462 AC: 4882 AN: 10558

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.393 AC: 26728 AN: 67938

Other (OTH) AF: 0.434 AC: 916 AN: 2112

Alfa AF: 0.420 Hom.: 24207

Bravo AF: 0.491

Asia WGS AF: 0.597 AC: 2077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.65
PhyloP100		-2.5
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: rs439783; hg19: chr17-31677160;