Variant 19-7851542-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001159944.3(EVI5L):c.862G>A(p.Val288Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,612,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

EVI5L
NM_001159944.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

Variant links:

Genes affected

EVI5L (HGNC:30464): (ecotropic viral integration site 5 like) Enables GTPase activator activity and small GTPase binding activity. Involved in negative regulation of cilium assembly and positive regulation of GTPase activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVI5L 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=0.022894353).

BS2

High AC in GnomAd4 at 101 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVI5L	NM_001159944.3 link	c.862G>A	p.Val288Ile	missense_variant	7/20	ENST00000538904.7	NP_001153416.1	Q96CN4-2
EVI5L	NM_145245.5 link	c.862G>A	p.Val288Ile	missense_variant	7/19		NP_660288.1	Q96CN4-1A0A384MR55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVI5L	ENST00000538904.7 link	c.862G>A	p.Val288Ile	missense_variant	7/20	1	NM_001159944.3	ENSP00000445905.1		Q96CN4-2

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000352

AC:

AN:

249690

Hom.:

AF XY:

0.000296

AC XY:

AN XY:

134952

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.000768

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000192

AC:

281

AN:

1460424

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

133

AN XY:

726462

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.000719

Gnomad4 ASJ exome

AF:

0.00173

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000891

Gnomad4 OTH exome

AF:

0.000481

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152228

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000402

Hom.:

Bravo

AF:

0.00104

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000179

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

Mar 01, 2024

The c.862G>A (p.V288I) alteration is located in exon 6 (coding exon 6) of the EVI5L gene. This alteration results from a G to A substitution at nucleotide position 862, causing the valine (V) at amino acid position 288 to be replaced by an isoleucine (I). 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

0.075

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.19

DEOGEN2

Benign

0.033

T;.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.023

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.10

N;N;.

PrimateAI

Benign

0.45

PROVEAN

Benign

0.090

N;N;.

REVEL

Benign

0.081

Sift

Benign

0.62

T;T;.

Sift4G

Benign

0.57

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.22

MVP

0.23

MPC

0.81

ClinPred

0.0099

GERP RS

3.7

Varity_R

0.046

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