Genetic Variant EVI5L:p.Arg262Cys (chr19-7851464-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001159944.3(EVI5L):c.784C>T(p.Arg262Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 1,460,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R262H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

EVI5L
NM_001159944.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00

Publications

3 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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 13 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.784C>T	p.Arg262Cys	missense	Exon 7 of 20	NP_001153416.1	Q96CN4-2
	EVI5L	NM_145245.5		c.784C>T	p.Arg262Cys	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.784C>T	p.Arg262Cys	missense	Exon 7 of 20	ENSP00000445905.1	Q96CN4-2
EVI5L	ENST00000270530.8	TSL:1	c.784C>T	p.Arg262Cys	missense	Exon 7 of 19	ENSP00000270530.3	Q96CN4-1
EVI5L	ENST00000962893.1		c.784C>T	p.Arg262Cys	missense	Exon 7 of 20	ENSP00000632952.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

250122

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460890

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726730

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111562

Other (OTH)

AF:

0.00

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

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

0.16

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

PhyloP100

6.0

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.21

Sift

Benign

0.12

Sift4G

Uncertain

0.040

Polyphen

0.99

Vest4

0.47

MutPred

0.47

Loss of disorder (P = 0.0097)

MVP

0.37

MPC

2.5

ClinPred

0.99

GERP RS

4.8

Varity_R

0.38

gMVP

0.44

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: 11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over