Variant chr21-32467842-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_058187.5(EVA1C):c.628C>G(p.Pro210Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000165 in 1,607,910 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P210R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 4 hom. )

Consequence

EVA1C
NM_058187.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

Variant links:

Genes affected

EVA1C (HGNC:13239): (eva-1 homolog C) Enables heparin binding activity. Colocalizes with extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

EVA1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038518548).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVA1C	NM_058187.5 linkuse as main transcript	c.628C>G	p.Pro210Ala	missense_variant	4/8	ENST00000300255.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVA1C	ENST00000300255.7 linkuse as main transcript	c.628C>G	p.Pro210Ala	missense_variant	4/8	1	NM_058187.5	P3	P58658-1

Frequencies

GnomAD3 genomes

AF:

0.0000725

AC:

AN:

151822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000395

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000361

AC:

AN:

244102

Hom.:

AF XY:

0.000378

AC XY:

AN XY:

132216

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.000921

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

Gnomad SAS exome

AF:

0.00126

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000144

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.000174

AC:

254

AN:

1455970

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

155

AN XY:

724330

show subpopulations

Gnomad4 AFR exome

AF:

0.0000907

Gnomad4 AMR exome

AF:

0.000780

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000622

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000724

AC:

AN:

151940

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000346

AC:

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

Jul 20, 2021

The c.628C>G (p.P210A) alteration is located in exon 4 (coding exon 4) of the EVA1C gene. This alteration results from a C to G substitution at nucleotide position 628, causing the proline (P) at amino acid position 210 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

0.069

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0093

T;T;.;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.039

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.11

T;T;T;T

Sift4G

Benign

0.062

T;D;T;T

Polyphen

0.96

D;P;.;.

Vest4

0.39

MVP

0.36

MPC

0.73

ClinPred

0.073

GERP RS

5.6

Varity_R

0.072

gMVP

0.55

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