Genetic Variant EVI5L:p.His470Tyr (chr19-7860594-C-T) – 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.1408C>T(p.His470Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000687 in 1,600,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

EVI5L
NM_001159944.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.06476906).

BS2

High AC in GnomAdExome4 at 9 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.1408C>T	p.His470Tyr	missense	Exon 14 of 20	NP_001153416.1	Q96CN4-2
	EVI5L	NM_145245.5		c.1375C>T	p.His459Tyr	missense	Exon 13 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.1408C>T	p.His470Tyr	missense	Exon 14 of 20	ENSP00000445905.1	Q96CN4-2
EVI5L	ENST00000270530.8	TSL:1	c.1375C>T	p.His459Tyr	missense	Exon 13 of 19	ENSP00000270530.3	Q96CN4-1
EVI5L	ENST00000962893.1		c.1408C>T	p.His470Tyr	missense	Exon 14 of 20	ENSP00000632952.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000443

AC:

AN:

225782

AF XY:

0.0000409

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000520

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000622

AC:

AN:

1447710

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

718982

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33286

American (AMR)

AF:

0.00

AC:

AN:

43022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25774

East Asian (EAS)

AF:

0.000178

AC:

AN:

39288

South Asian (SAS)

AF:

0.0000119

AC:

AN:

84090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105950

Other (OTH)

AF:

0.0000167

AC:

AN:

59898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000131

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41584

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000331

AC:

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

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.052

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

M_CAP

Benign

0.0062

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

4.1

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.4

REVEL

Benign

0.038

Sift

Benign

0.067

Sift4G

Benign

0.26

Polyphen

0.83

Vest4

0.29

MutPred

0.22

Gain of phosphorylation at H459 (P = 0.026)

MVP

0.25

MPC

1.7

ClinPred

0.14

GERP RS

4.4

PromoterAI

0.073

Neutral

(source)

Varity_R

0.20

gMVP

0.31

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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