12-50073986-G-A

Position:

• chr12-50073986-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000552438.5(ASIC1):​c.402G>A​(p.Pro134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,535,362 control chromosomes in the GnomAD database, including 117,820 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 0.32 (9223 hom., cov: 32)
  • Exomes 𝑓: 0.39 (108597 hom.)
• Consequence: ASIC1 ENST00000552438.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85

Genes affected

ASIC1 (HGNC:100): (acid sensing ion channel subunit 1) This gene encodes a member of the acid-sensing ion channel (ASIC) family of proteins, which are part of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. Members of the ASIC family are sensitive to amiloride and function in neurotransmission. The encoded proteins function in learning, pain transduction, touch sensation, and development of memory and fear. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-2.85 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIC1	NM_001095.4	c.559-3227G>A		intron_variant		ENST00000447966.7	NP_001086.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIC1	ENST00000447966.7	c.559-3227G>A		intron_variant		1	NM_001095.4	ENSP00000400228	P1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48723 AN: 151960 Hom.: 9221 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.0763

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.347

GnomAD3 exomes AF: 0.334 AC: 44735 AN: 134106 Hom.: 8474 AF XY: 0.332 AC XY: 24208 AN XY: 73018

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.0752

Gnomad SAS exome AF: 0.254

Gnomad FIN exome AF: 0.449

Gnomad NFE exome AF: 0.421

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.387 AC: 535431 AN: 1383282 Hom.: 108597 Cov.: 65 AF XY: 0.384 AC XY: 262409 AN XY: 682568

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.0669

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.415

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.320 AC: 48737 AN: 152080 Hom.: 9223 Cov.: 32 AF XY: 0.321 AC XY: 23837 AN XY: 74338

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.0763

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.346

Alfa AF: 0.374 Hom.: 6593

Bravo AF: 0.305

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.60
DANN	Benign	0.81

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: rs706793; hg19: chr12-50467769; COSMIC: COSV57317760; COSMIC: COSV57317760;