Genetic Variant NM_001159944.3:c.862G>A (chr19-7851542-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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. 16/22 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

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022894353).

BS2

High AC in GnomAd4 at 101 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI5L	NM_001159944.3	MANE Select	c.862G>A	p.Val288Ile	missense	Exon 7 of 20	NP_001153416.1	Q96CN4-2
	EVI5L	NM_145245.5		c.862G>A	p.Val288Ile	missense	Exon 7 of 19	NP_660288.1	Q96CN4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EVI5L	ENST00000538904.7	TSL:1 MANE Select	c.862G>A	p.Val288Ile	missense	Exon 7 of 20	ENSP00000445905.1	Q96CN4-2
EVI5L	ENST00000270530.8	TSL:1	c.862G>A	p.Val288Ile	missense	Exon 7 of 19	ENSP00000270530.3	Q96CN4-1
EVI5L	ENST00000962893.1		c.862G>A	p.Val288Ile	missense	Exon 7 of 20	ENSP00000632952.1

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

GnomAD2 exomes

AF:

0.000352

AC:

AN:

249690

AF XY:

0.000296

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 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

African (AFR)

AF:

0.00212

AC:

AN:

33444

American (AMR)

AF:

0.000719

AC:

AN:

44476

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

26086

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39628

South Asian (SAS)

AF:

0.00

AC:

AN:

85860

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000891

AC:

AN:

1111414

Other (OTH)

AF:

0.000481

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152228

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

41540

American (AMR)

AF:

0.00150

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67998

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.033

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.76

M_CAP

Benign

0.0054

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.10

PhyloP100

3.2

PrimateAI

Benign

0.45

PROVEAN

Benign

0.090

REVEL

Benign

0.081

Sift

Benign

0.62

Sift4G

Benign

0.57

Polyphen

0.0

Vest4

0.22

MVP

0.23

MPC

0.81

ClinPred

0.0099

GERP RS

3.7

Varity_R

0.046

gMVP

0.18

Mutation Taster

=91/9

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over