rs9892479

Variant names:

• chr17-33094883-G-T
• rs9892479
• NM_183377.2:c.860-5893C>A

Variant summary

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

The NM_183377.2(ASIC2):​c.860-5893C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 152,258 control chromosomes in the GnomAD database, including 129 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 0.040 (129 hom., cov: 33)
• Consequence: ASIC2 NM_183377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• 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=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0398 (6067/152258) while in subpopulation NFE AF = 0.0474 (3225/68022). AF 95% confidence interval is 0.046. There are 129 homozygotes in GnomAd4. There are 2886 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 6067 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC2	NM_183377.2	c.860-5893C>A		intron_variant	Intron 2 of 9	ENST00000225823.7	NP_899233.1
ASIC2	NM_001094.5	c.707-5893C>A		intron_variant	Intron 2 of 9		NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000225823.7	c.860-5893C>A		intron_variant	Intron 2 of 9	1	NM_183377.2	ENSP00000225823.2
ASIC2	ENST00000359872.6	c.707-5893C>A		intron_variant	Intron 2 of 9	1		ENSP00000352934.6
ASIC2	ENST00000448983.1	n.265-5893C>A		intron_variant	Intron 3 of 6	3

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 6065 AN: 152140 Hom.: 129 Cov.: 33

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0264

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0398 AC: 6067 AN: 152258 Hom.: 129 Cov.: 33 AF XY: 0.0388 AC XY: 2886 AN XY: 74442

African (AFR) AF: 0.0405 AC: 1685 AN: 41558

American (AMR) AF: 0.0330 AC: 505 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.0266 AC: 128 AN: 4814

European-Finnish (FIN) AF: 0.0227 AC: 241 AN: 10604

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0474 AC: 3225 AN: 68022

Other (OTH) AF: 0.0431 AC: 91 AN: 2112

Alfa AF: 0.0422 Hom.: 235

Bravo AF: 0.0393

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		0.024
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: rs9892479; hg19: chr17-31421901;