Variant chr14-100135929-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016337.3(EVL):c.925C>G(p.Pro309Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00593 in 1,613,906 control chromosomes in the GnomAD database, including 494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 255 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 239 hom. )

Consequence

EVL
NM_016337.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.04

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015016794).

BP6

Variant 14-100135929-C-G is Benign according to our data. Variant chr14-100135929-C-G is described in ClinVar as [Benign]. Clinvar id is 710043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVL	NM_016337.3 linkuse as main transcript	c.925C>G	p.Pro309Ala	missense_variant	9/14	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.925C>G	p.Pro309Ala	missense_variant	9/14	1	NM_016337.3	ENSP00000376652	P1	Q9UI08-2

Frequencies

GnomAD3 genomes

AF:

0.0317

AC:

4830

AN:

152198

Hom.:

256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.00819

AC:

2058

AN:

251156

Hom.:

110

AF XY:

0.00578

AC XY:

785

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.00625

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00324

AC:

4732

AN:

1461590

Hom.:

239

Cov.:

AF XY:

0.00274

AC XY:

1995

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.00698

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000236

Gnomad4 OTH exome

AF:

0.00677

GnomAD4 genome

AF:

0.0318

AC:

4838

AN:

152316

Hom.:

255

Cov.:

AF XY:

0.0298

AC XY:

2222

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0217

Alfa

AF:

0.00967

Hom.:

Bravo

AF:

0.0362

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.101

AC:

444

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00995

AC:

1208

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Uncertain

0.44

T;.;.;T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.84

T;T;T;T;D

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.;.;.;.

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.2

D;D;D;D;D

REVEL

Benign

0.080

Sift

Benign

0.041

D;D;D;D;D

Sift4G

Benign

0.41

T;T;T;T;T

Polyphen

0.20

B;.;B;.;.

Vest4

0.29

MVP

0.47

MPC

0.53

ClinPred

0.027

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.20

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