12-50073986-G-A

Variant names:

• chr12-50073986-G-A
• rs706793
• ENST00000552438.5:c.402G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001256830.2(ASIC1):​c.402G>A​(p.Pro134Pro) 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 NM_001256830.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256830.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC1	NM_001095.4	MANE Select	c.559-3227G>A		intron	N/A	NP_001086.2
	ASIC1	NM_001256830.2		c.402G>A	p.Pro134Pro	synonymous	Exon 1 of 10	NP_001243759.1	P78348-3
	ASIC1	NM_020039.4		c.559-3227G>A		intron	N/A	NP_064423.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC1	ENST00000552438.5	TSL:1	c.402G>A	p.Pro134Pro	synonymous	Exon 1 of 10	ENSP00000450247.1	P78348-3
	ASIC1	ENST00000447966.7	TSL:1 MANE Select	c.559-3227G>A		intron	N/A	ENSP00000400228.3	P78348-2
	ASIC1	ENST00000228468.8	TSL:1	c.559-3227G>A		intron	N/A	ENSP00000228468.4	P78348-1

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

GnomAD2 exomes AF: 0.334 AC: 44735 AN: 134106 AF XY: 0.332

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 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

African (AFR) AF: 0.128 AC: 4042 AN: 31576

American (AMR) AF: 0.305 AC: 10864 AN: 35656

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 12014 AN: 25160

East Asian (EAS) AF: 0.0669 AC: 2390 AN: 35730

South Asian (SAS) AF: 0.259 AC: 20542 AN: 79192

European-Finnish (FIN) AF: 0.438 AC: 14852 AN: 33898

Middle Eastern (MID) AF: 0.413 AC: 2348 AN: 5686

European-Non Finnish (NFE) AF: 0.415 AC: 447263 AN: 1078514

Other (OTH) AF: 0.365 AC: 21116 AN: 57870

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

African (AFR) AF: 0.142 AC: 5895 AN: 41512

American (AMR) AF: 0.339 AC: 5181 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1652 AN: 3460

East Asian (EAS) AF: 0.0763 AC: 395 AN: 5180

South Asian (SAS) AF: 0.249 AC: 1201 AN: 4824

European-Finnish (FIN) AF: 0.450 AC: 4755 AN: 10570

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.418 AC: 28403 AN: 67938

Other (OTH) AF: 0.346 AC: 731 AN: 2112

Alfa AF: 0.374 Hom.: 7262

Bravo AF: 0.305

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.60
DANN	Benign	0.81
PhyloP100		-2.9
PromoterAI		-0.0052	Neutral
Mutation Taster		=98/2	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: rs706793; hg19: chr12-50467769; COSMIC: COSV57317760; COSMIC: COSV57317760;