chr17-33960430-G-A

Variant names:

• chr17-33960430-G-A
• rs11650066
• ENST00000359872.6:c.555+195548C>T

Variant summary

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

The ENST00000359872.6(ASIC2):​c.555+195548C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,090 control chromosomes in the GnomAD database, including 9,124 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 0.34 (9124 hom., cov: 32)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• Publications: 8 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]

ENSG00000279668 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359872.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	NM_001094.5		c.555+195548C>T		intron	N/A	NP_001085.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000359872.6	TSL:1	c.555+195548C>T		intron	N/A	ENSP00000352934.6
	ENSG00000279668	ENST00000584758.2	TSL:5	n.189-23608C>T		intron	N/A
	ENSG00000265356	ENST00000636421.1	TSL:5	n.459-23608C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51953 AN: 151970 Hom.: 9107 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.342 AC: 52016 AN: 152090 Hom.: 9124 Cov.: 32 AF XY: 0.339 AC XY: 25224 AN XY: 74336

African (AFR) AF: 0.379 AC: 15725 AN: 41474

American (AMR) AF: 0.285 AC: 4350 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1344 AN: 3472

East Asian (EAS) AF: 0.175 AC: 906 AN: 5170

South Asian (SAS) AF: 0.242 AC: 1168 AN: 4822

European-Finnish (FIN) AF: 0.328 AC: 3474 AN: 10576

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23728 AN: 67972

Other (OTH) AF: 0.341 AC: 720 AN: 2110

Alfa AF: 0.346 Hom.: 43395

Bravo AF: 0.342

Asia WGS AF: 0.233 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.34
PhyloP100		0.56
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: rs11650066; hg19: chr17-32287449;