NM_001350197.2:c.1884G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q628R) has been classified as Uncertain significance.

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

Publications

35 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EVI5	NM_001350197.2 link	c.1884G>T	p.Gln628His	missense_variant	Exon 17 of 20	ENST00000684568.2	NP_001337126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVI5	ENST00000684568.2 link	c.1884G>T	p.Gln628His	missense_variant	Exon 17 of 20		NM_001350197.2	ENSP00000506999.1		A0A804HIC4

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

GnomAD2 exomes

AF:

0.195

AC:

47734

AN:

244648

AF XY:

0.197

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 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

African (AFR)

AF:

0.0895

AC:

2967

AN:

33160

American (AMR)

AF:

0.172

AC:

7482

AN:

43626

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

7347

AN:

25960

East Asian (EAS)

AF:

0.0174

AC:

686

AN:

39518

South Asian (SAS)

AF:

0.120

AC:

10132

AN:

84694

European-Finnish (FIN)

AF:

0.241

AC:

12689

AN:

52696

Middle Eastern (MID)

AF:

0.240

AC:

1382

AN:

5750

European-Non Finnish (NFE)

AF:

0.254

AC:

281422

AN:

1106490

Other (OTH)

AF:

0.227

AC:

13612

AN:

60070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

11691

23382

35073

46764

58455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.196

AC:

29711

AN:

151926

Hom.:

3454

Cov.:

AF XY:

0.194

AC XY:

14423

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.0945

AC:

3919

AN:

41474

American (AMR)

AF:

0.222

AC:

3390

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

945

AN:

3464

East Asian (EAS)

AF:

0.0241

AC:

125

AN:

5176

South Asian (SAS)

AF:

0.120

AC:

578

AN:

4814

European-Finnish (FIN)

AF:

0.257

AC:

2701

AN:

10516

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17322

AN:

67926

Other (OTH)

AF:

0.230

AC:

486

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1166

2332

3497

4663

5829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.234

Hom.:

19963

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

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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;.

PhyloP100

0.72

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

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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NM_001350197.2:c.1884G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over