Variant 12-50080626-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020039.4(ASIC1):c.1334A>G(p.His445Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,614,166 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 6 hom. )

Consequence

ASIC1
NM_020039.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.303

Variant links:

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]

ASIC1 links:

ASIC1 (HGNC:):

ASIC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022660792).

BP6

Variant 12-50080626-A-G is Benign according to our data. Variant chr12-50080626-A-G is described in ClinVar as [Benign]. Clinvar id is 779524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-50080626-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0071 (1081/152290) while in subpopulation AFR AF= 0.0241 (1003/41558). AF 95% confidence interval is 0.0229. There are 10 homozygotes in gnomad4. There are 509 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1081 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIC1	NM_001095.4 linkuse as main transcript	c.1297+37A>G		intron_variant		ENST00000447966.7	NP_001086.2	P78348-2A8K1U5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIC1	ENST00000447966.7 linkuse as main transcript	c.1297+37A>G		intron_variant		1	NM_001095.4	ENSP00000400228.3		P78348-2

Frequencies

GnomAD3 genomes

AF:

0.00712

AC:

1083

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00862

GnomAD3 exomes

AF:

0.00174

AC:

438

AN:

251458

Hom.:

AF XY:

0.00122

AC XY:

166

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0249

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000658

AC:

962

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000569

AC XY:

414

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0237

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00710

AC:

1081

AN:

152290

Hom.:

Cov.:

AF XY:

0.00684

AC XY:

509

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0241

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00853

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.00863

ESP6500AA

AF:

0.0266

AC:

117

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00208

AC:

253

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.0

DANN

Uncertain

0.98

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.12

REVEL

Benign

0.051

Sift

Benign

0.46

Sift4G

Benign

0.18

Polyphen

0.0020

Vest4

0.070

MVP

0.42

MPC

1.3

ClinPred

0.00096

GERP RS

3.0

gMVP

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over