rs4795846

Positions:

• chr17-34037703-T-C

Variant summary

Our verdict is Benign. Variant got -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

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)

LOC107987247 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LOC107987247	XR_002958159.2	n.2247+10629A>G		intron_variant, non_coding_transcript_variant
ASIC2	NM_001094.5	c.555+118275A>G		intron_variant			NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIC2	ENST00000359872.6	c.555+118275A>G		intron_variant		1		ENSP00000352934	P1
TLK2P1	ENST00000530992.1	n.2170A>G		non_coding_transcript_exon_variant	1/1
	ENST00000636506.1	n.746+33114A>G		intron_variant, non_coding_transcript_variant		5
	ENST00000637478.1	n.1716+33114A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.857

Gnomad4 AMR exome AF: 0.567

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.503

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.383

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.409

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

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.473

Alfa AF: 0.476 Hom.: 4240

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4795846; hg19: chr17-32364722; COSMIC: COSV63308327;