Variant chr19-7861980-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001159944.3(EVI5L):c.1606C>T(p.Leu536Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000574 in 1,549,298 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 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

EVI5L
NM_001159944.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15889135).

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVI5L	NM_001159944.3 link	c.1606C>T	p.Leu536Phe	missense_variant	15/20	ENST00000538904.7	NP_001153416.1	Q96CN4-2
EVI5L	NM_145245.5 link	c.1573C>T	p.Leu525Phe	missense_variant	14/19		NP_660288.1	Q96CN4-1A0A384MR55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EVI5L	ENST00000538904.7 link	c.1606C>T	p.Leu536Phe	missense_variant	15/20	1	NM_001159944.3	ENSP00000445905.1	Q96CN4-2
EVI5L	ENST00000270530.8 link	c.1573C>T	p.Leu525Phe	missense_variant	14/19	1		ENSP00000270530.3	Q96CN4-1
EVI5L	ENST00000601766.1 link	c.208C>T	p.Leu70Phe	missense_variant	2/4	3		ENSP00000470145.1	M0QYX4

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152228

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000101

AC:

AN:

148510

Hom.:

AF XY:

0.000101

AC XY:

AN XY:

79116

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.0000408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000177

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000164

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000573

AC:

AN:

1397070

Hom.:

Cov.:

AF XY:

0.0000653

AC XY:

AN XY:

689030

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.0000281

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000101

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000566

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000900

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.1606C>T (p.L536F) alteration is located in exon 14 (coding exon 14) of the EVI5L gene. This alteration results from a C to T substitution at nucleotide position 1606, causing the leucine (L) at amino acid position 536 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;.;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.053

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.1

M;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.1

D;D;.

REVEL

Benign

0.074

Sift

Uncertain

0.0040

D;D;.

Sift4G

Uncertain

0.043

D;D;T

Polyphen

0.96

D;.;.

Vest4

0.27

MutPred

0.25

Gain of methylation at K526 (P = 0.0365);.;.;

MVP

0.30

MPC

1.5

ClinPred

0.46

GERP RS

4.4

Varity_R

0.23

gMVP

0.60

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