12-50077326-C-T

Position:

• chr12-50077326-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001095.4(ASIC1):​c.672C>T​(p.Ile224=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 1,614,170 control chromosomes in the GnomAD database, including 407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (208 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (199 hom.)
• Consequence: ASIC1 NM_001095.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.130

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=-0.27).
• BP6: Variant 12-50077326-C-T is Benign according to our data. Variant chr12-50077326-C-T is described in ClinVar as [Benign]. Clinvar id is 783660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC1	NM_001095.4	c.672C>T	p.Ile224=	synonymous_variant	4/12	ENST00000447966.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC1	ENST00000447966.7	c.672C>T	p.Ile224=	synonymous_variant	4/12	1	NM_001095.4	P1

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4262 AN: 152184 Hom.: 207 Cov.: 32

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0191

GnomAD3 exomes AF: 0.00736 AC: 1850 AN: 251312 Hom.: 88 AF XY: 0.00488 AC XY: 663 AN XY: 135874

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00293 AC: 4281 AN: 1461868 Hom.: 199 Cov.: 31 AF XY: 0.00247 AC XY: 1798 AN XY: 727238

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.00492

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.0000728

Gnomad4 OTH exome AF: 0.00667

GnomAD4 genome AF: 0.0281 AC: 4280 AN: 152302 Hom.: 208 Cov.: 32 AF XY: 0.0274 AC XY: 2037 AN XY: 74470

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0133 Hom.: 38

Bravo AF: 0.0318

Asia WGS AF: 0.00751 AC: 27 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	9.0
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61731226; hg19: chr12-50471109;