rs4795846

Variant names:

• chr17-34037703-T-C
• rs4795846
• ENST00000359872.6:c.555+118275A>G

Variant summary

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

The ENST00000359872.6(ASIC2):​c.555+118275A>G variant causes a intron change. The variant allele was found at a frequency of 0.409 in 1,603,926 control chromosomes in the GnomAD database, including 145,319 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 (23908 hom., cov: 31)
  • Exomes 𝑓: 0.40 (121411 hom.)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93
• Publications: 5 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]

TLK2P1 (HGNC:18048): (tousled like kinase 2 pseudogene 1)

ENSG00000265356 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLK2P1		n.34037703T>C		intragenic_variant
ASIC2	NM_001094.5	c.555+118275A>G		intron_variant	Intron 1 of 9		NP_001085.2
LOC107987247	XR_002958159.2	n.2247+10629A>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000359872.6	c.555+118275A>G		intron_variant	Intron 1 of 9	1		ENSP00000352934.6
TLK2P1	ENST00000530992.1	n.2170A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000265356	ENST00000636421.1	n.458+3531A>G		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79266 AN: 151752 Hom.: 23848 Cov.: 31

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.397 AC: 576625 AN: 1452056 Hom.: 121411 Cov.: 42 AF XY: 0.396 AC XY: 285896 AN XY: 721946

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.857 AC: 28602 AN: 33374

American (AMR) AF: 0.567 AC: 25214 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 9927 AN: 26038

East Asian (EAS) AF: 0.503 AC: 19899 AN: 39526

South Asian (SAS) AF: 0.438 AC: 37687 AN: 86006

European-Finnish (FIN) AF: 0.383 AC: 20437 AN: 53306

Middle Eastern (MID) AF: 0.370 AC: 2094 AN: 5666

European-Non Finnish (NFE) AF: 0.370 AC: 408161 AN: 1103554

Other (OTH) AF: 0.409 AC: 24604 AN: 60086

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.523 AC: 79383 AN: 151870 Hom.: 23908 Cov.: 31 AF XY: 0.520 AC XY: 38583 AN XY: 74220

African (AFR) AF: 0.839 AC: 34736 AN: 41384

American (AMR) AF: 0.502 AC: 7656 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3466

East Asian (EAS) AF: 0.509 AC: 2626 AN: 5160

South Asian (SAS) AF: 0.427 AC: 2052 AN: 4802

European-Finnish (FIN) AF: 0.376 AC: 3964 AN: 10550

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25510 AN: 67932

Other (OTH) AF: 0.473 AC: 997 AN: 2108

Alfa AF: 0.489 Hom.: 5026

Bravo AF: 0.549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.9
DANN	Benign	0.62
PhyloP100		3.9
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: rs4795846; hg19: chr17-32364722; COSMIC: COSV63308327;