Variant 1-36322593-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001304762.2(EVA1B):c.200A>C(p.Asp67Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EVA1B
NM_001304762.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

Variant links:

Genes affected

EVA1B (HGNC:25558): (eva-1 homolog B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVA1B links:

SH3D21 (HGNC:26236): (SH3 domain containing 21) Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SH3D21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0692887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVA1B	NM_001304762.2 linkuse as main transcript	c.200A>C	p.Asp67Ala	missense_variant	3/3	ENST00000490466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVA1B	ENST00000490466.2 linkuse as main transcript	c.200A>C	p.Asp67Ala	missense_variant	3/3	2	NM_001304762.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

138210

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000760

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000111

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.09e-7

AC:

AN:

1409764

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.17e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000130

AC:

AN:

138210

Hom.:

Cov.:

AF XY:

0.000209

AC XY:

AN XY:

66978

show subpopulations

Gnomad4 AFR

AF:

0.000219

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000760

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000111

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000749

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2021

The c.200A>C (p.D67A) alteration is located in exon 3 (coding exon 2) of the EVA1B gene. This alteration results from a A to C substitution at nucleotide position 200, causing the aspartic acid (D) at amino acid position 67 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.012

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.32

M_CAP

Benign

0.0065

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.34

REVEL

Benign

0.055

Sift

Benign

0.69

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.097

MutPred

0.18

Gain of helix (P = 0.0425);

MVP

0.11

MPC

0.93

ClinPred

0.11

GERP RS

2.1

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.066

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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