Variant 1-92607671-C-A 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_001350197.2(EVI5):c.1884G>T(p.Gln628His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,603,890 control chromosomes in the GnomAD database, including 45,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3454 hom., cov: 31)

Exomes 𝑓: 0.23 ( 42127 hom. )

Consequence

EVI5
NM_001350197.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.721

Variant links:

Genes affected

EVI5 (HGNC:3501): (ecotropic viral integration site 5) Enables GTPase activator activity and small GTPase binding activity. Involved in positive regulation of GTPase activity and retrograde transport, endosome to Golgi. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

EVI5 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=0.0014106333).

BP6

Variant 1-92607671-C-A is Benign according to our data. Variant chr1-92607671-C-A is described in ClinVar as [Benign]. Clinvar id is 402837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVI5	NM_001350197.2 linkuse as main transcript	c.1884G>T	p.Gln628His	missense_variant	17/20	ENST00000684568.2	NP_001337126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVI5	ENST00000684568.2 linkuse as main transcript	c.1884G>T	p.Gln628His	missense_variant	17/20		NM_001350197.2	ENSP00000506999	P1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29697

AN:

151808

Hom.:

3454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0945

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.0239

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.234

GnomAD3 exomes

AF:

0.195

AC:

47734

AN:

244648

Hom.:

5390

AF XY:

0.197

AC XY:

25994

AN XY:

132264

show subpopulations

Gnomad AFR exome

AF:

0.0892

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.0217

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.241

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.233

AC:

337719

AN:

1451964

Hom.:

42127

Cov.:

AF XY:

0.230

AC XY:

166281

AN XY:

722290

show subpopulations

Gnomad4 AFR exome

AF:

0.0895

Gnomad4 AMR exome

AF:

0.172

Gnomad4 ASJ exome

AF:

0.283

Gnomad4 EAS exome

AF:

0.0174

Gnomad4 SAS exome

AF:

0.120

Gnomad4 FIN exome

AF:

0.241

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.196

AC:

29711

AN:

151926

Hom.:

3454

Cov.:

AF XY:

0.194

AC XY:

14423

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.0945

Gnomad4 AMR

AF:

0.222

Gnomad4 ASJ

AF:

0.273

Gnomad4 EAS

AF:

0.0241

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.255

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.240

Hom.:

11469

Bravo

AF:

0.187

TwinsUK

AF:

0.261

AC:

969

ALSPAC

AF:

0.256

AC:

988

ESP6500AA

AF:

0.106

AC:

467

ESP6500EA

AF:

0.257

AC:

2206

ExAC

AF:

0.194

AC:

23595

Asia WGS

AF:

0.0830

AC:

291

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

D;D

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

0.00017

P;P;P

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.7

D;.

REVEL

Benign

0.11

Sift

Benign

0.049

D;.

Sift4G

Uncertain

0.049

D;D

Polyphen

0.0030

B;.

Vest4

0.10

MutPred

0.18

.;Loss of ubiquitination at K625 (P = 0.091);

MPC

0.14

ClinPred

0.032

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.34

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