Variant 2-75493462-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001135032.2(EVA1A):c.233G>A(p.Ser78Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00044 in 1,614,254 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 4 hom. )

Consequence

EVA1A
NM_001135032.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.84

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057659745).

BP6

Variant 2-75493462-C-T is Benign according to our data. Variant chr2-75493462-C-T is described in ClinVar as [Benign]. Clinvar id is 3052878.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EVA1A	NM_001135032.2 linkuse as main transcript	c.233G>A	p.Ser78Asn	missense_variant	4/4	ENST00000393913.8
EVA1A	NM_001369524.1 linkuse as main transcript	c.233G>A	p.Ser78Asn	missense_variant	6/6
EVA1A	NM_001369525.1 linkuse as main transcript	c.233G>A	p.Ser78Asn	missense_variant	5/5
EVA1A	NM_032181.3 linkuse as main transcript	c.233G>A	p.Ser78Asn	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVA1A	ENST00000393913.8 linkuse as main transcript	c.233G>A	p.Ser78Asn	missense_variant	4/4	1	NM_001135032.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00630

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000896

AC:

225

AN:

251246

Hom.:

AF XY:

0.000810

AC XY:

110

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00781

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000422

AC:

617

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000411

AC XY:

299

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00730

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000610

AC:

AN:

152386

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74530

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00630

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000281

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000939

AC:

114

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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

Aug 28, 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

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.0066

T;T;T;T;T;T;.

Eigen

Benign

-0.015

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.79

M_CAP

Benign

0.0053

MetaRNN

Benign

0.0058

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;L;.;L;.;.

MutationTaster

Benign

0.57

D;D;D;D;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.2

N;N;N;N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.46

T;T;T;T;T;T;T

Sift4G

Benign

0.22

T;T;T;T;T;.;T

Polyphen

0.18

B;B;B;.;B;.;.

Vest4

0.059

MVP

0.58

MPC

0.44

ClinPred

0.053

GERP RS

5.0

Varity_R

0.061

gMVP

0.18

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