rs117364231

Positions:

• chr17-33979404-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000359872.6(ASIC2):​c.555+176574G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 152,244 control chromosomes in the GnomAD database, including 40 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 0.018 (40 hom., cov: 32)
• Consequence: ASIC2 ENST00000359872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0176 (2681/152244) while in subpopulation EAS AF= 0.0518 (268/5172). AF 95% confidence interval is 0.0467. There are 40 homozygotes in gnomad4. There are 1276 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2681 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107985038	XR_001752840.2	n.221+7741G>A		intron_variant, non_coding_transcript_variant
ASIC2	NM_001094.5	c.555+176574G>A		intron_variant			NP_001085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000582685.1	n.217-1341C>T		intron_variant, non_coding_transcript_variant		3
	ENST00000659958.1	n.130+4783G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2683 AN: 152126 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.00367

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.00989

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0176 AC: 2681 AN: 152244 Hom.: 40 Cov.: 32 AF XY: 0.0171 AC XY: 1276 AN XY: 74452

Gnomad4 AFR AF: 0.00366

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.0518

Gnomad4 SAS AF: 0.0240

Gnomad4 FIN AF: 0.00989

Gnomad4 NFE AF: 0.0243

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0198 Hom.: 5

Bravo AF: 0.0175

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.45

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: rs117364231; hg19: chr17-32306423;