Variant 2-75493246-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001135032.2(EVA1A):c.449G>A(p.Arg150His) variant causes a missense change. The variant allele was found at a frequency of 0.0469 in 1,611,076 control chromosomes in the GnomAD database, including 2,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.052 ( 245 hom., cov: 33)

Exomes 𝑓: 0.046 ( 1794 hom. )

Consequence

EVA1A
NM_001135032.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.07

Variant links:

Genes affected

EVA1A (HGNC:25816): (eva-1 homolog A, regulator of programmed cell death) Predicted to be involved in apoptotic process and autophagy. Located in intracellular membrane-bounded organelle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVA1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016549826).

BP6

Variant 2-75493246-C-T is Benign according to our data. Variant chr2-75493246-C-T is described in ClinVar as [Benign]. Clinvar id is 3056113.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EVA1A	NM_001135032.2 linkuse as main transcript	c.449G>A	p.Arg150His	missense_variant	4/4	ENST00000393913.8
EVA1A	NM_001369524.1 linkuse as main transcript	c.449G>A	p.Arg150His	missense_variant	6/6
EVA1A	NM_001369525.1 linkuse as main transcript	c.449G>A	p.Arg150His	missense_variant	5/5
EVA1A	NM_032181.3 linkuse as main transcript	c.449G>A	p.Arg150His	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVA1A	ENST00000393913.8 linkuse as main transcript	c.449G>A	p.Arg150His	missense_variant	4/4	1	NM_001135032.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0516

AC:

7860

AN:

152182

Hom.:

245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0681

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.0390

Gnomad ASJ

AF:

0.0611

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0406

Gnomad FIN

AF:

0.0200

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0508

Gnomad OTH

AF:

0.0588

GnomAD3 exomes

AF:

0.0412

AC:

10143

AN:

246392

Hom.:

267

AF XY:

0.0425

AC XY:

5678

AN XY:

133526

show subpopulations

Gnomad AFR exome

AF:

0.0685

Gnomad AMR exome

AF:

0.0233

Gnomad ASJ exome

AF:

0.0580

Gnomad EAS exome

AF:

0.000437

Gnomad SAS exome

AF:

0.0368

Gnomad FIN exome

AF:

0.0234

Gnomad NFE exome

AF:

0.0523

Gnomad OTH exome

AF:

0.0497

GnomAD4 exome

AF:

0.0464

AC:

67723

AN:

1458776

Hom.:

1794

Cov.:

AF XY:

0.0464

AC XY:

33636

AN XY:

725410

show subpopulations

Gnomad4 AFR exome

AF:

0.0713

Gnomad4 AMR exome

AF:

0.0245

Gnomad4 ASJ exome

AF:

0.0602

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0379

Gnomad4 FIN exome

AF:

0.0236

Gnomad4 NFE exome

AF:

0.0494

Gnomad4 OTH exome

AF:

0.0466

GnomAD4 genome

AF:

0.0517

AC:

7867

AN:

152300

Hom.:

245

Cov.:

AF XY:

0.0491

AC XY:

3660

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0680

Gnomad4 AMR

AF:

0.0391

Gnomad4 ASJ

AF:

0.0611

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0406

Gnomad4 FIN

AF:

0.0200

Gnomad4 NFE

AF:

0.0508

Gnomad4 OTH

AF:

0.0587

Alfa

AF:

0.0506

Hom.:

535

Bravo

AF:

0.0539

TwinsUK

AF:

0.0472

AC:

175

ALSPAC

AF:

0.0501

AC:

193

ESP6500AA

AF:

0.0640

AC:

281

ESP6500EA

AF:

0.0509

AC:

437

ExAC

AF:

0.0438

AC:

5310

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

EVA1A-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.36

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.0034

T;T;T;T;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

0.0017

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

M;M;M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.56

N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.15

T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

1.0

D;D;D;.;D

Vest4

0.23

MPC

1.3

ClinPred

0.027

GERP RS

4.8

Varity_R

0.12

gMVP

0.58

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