Variant 14-100128659-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_016337.3(EVL):c.628G>A(p.Gly210Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,245,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000032 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

EVL
NM_016337.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

Variant links:

Genes affected

EVL (HGNC:20234): (Enah/Vasp-like) Predicted to enable SH3 domain binding activity and profilin binding activity. Involved in negative regulation of epithelial cell migration; negative regulation of ruffle assembly; and positive regulation of stress fiber assembly. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.39096224).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVL	NM_016337.3 linkuse as main transcript	c.628G>A	p.Gly210Arg	missense_variant	6/14	ENST00000392920.8	NP_057421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVL	ENST00000392920.8 linkuse as main transcript	c.628G>A	p.Gly210Arg	missense_variant	6/14	1	NM_016337.3	ENSP00000376652	P1	Q9UI08-2

Frequencies

GnomAD3 genomes

AF:

0.0000322

AC:

AN:

124280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000300

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000326

Gnomad OTH

AF:

0.000577

GnomAD3 exomes

AF:

0.00000883

AC:

AN:

226502

Hom.:

AF XY:

0.00000807

AC XY:

AN XY:

123944

show subpopulations

Gnomad AFR exome

AF:

0.0000728

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:

0.00

Gnomad NFE exome

AF:

0.00000987

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1121200

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

558258

show subpopulations

Gnomad4 AFR exome

AF:

0.000162

Gnomad4 AMR exome

AF:

0.0000276

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000582

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000103

Gnomad4 OTH exome

AF:

0.0000243

GnomAD4 genome

AF:

0.0000322

AC:

AN:

124280

Hom.:

Cov.:

AF XY:

0.0000342

AC XY:

AN XY:

58458

show subpopulations

Gnomad4 AFR

AF:

0.0000300

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000326

Gnomad4 OTH

AF:

0.000577

ExAC

AF:

0.00000827

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

Jun 29, 2023

The c.628G>A (p.G210R) alteration is located in exon 6 (coding exon 6) of the EVL gene. This alteration results from a G to A substitution at nucleotide position 628, causing the glycine (G) at amino acid position 210 to be replaced by an arginine (R). 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

Uncertain

0.54

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.51

D;.;.;T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.93

D;D;D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.7

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.4

D;D;D;D;D

REVEL

Benign

0.28

Sift

Benign

0.31

T;T;T;D;D

Sift4G

Uncertain

0.012

D;D;D;D;D

Polyphen

0.99

D;.;D;.;.

Vest4

0.67

MutPred

0.26

Gain of catalytic residue at P203 (P = 0.0047);.;.;.;.;

MVP

0.77

MPC

1.1

ClinPred

0.60

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.30

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