rs16895517

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142800.2(EYS):c.5617C>G(p.Leu1873Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,547,842 control chromosomes in the GnomAD database, including 13,774 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 913 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12861 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.00600

Variant links:

Genes affected

EYS (HGNC:21555): (eyes shut homolog) The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

EYS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017262399).

BP6

Variant 6-64590250-G-C is Benign according to our data. Variant chr6-64590250-G-C is described in ClinVar as [Benign]. Clinvar id is 93618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-64590250-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.5617C>G	p.Leu1873Val	missense_variant	Exon 26 of 43	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.5617C>G	p.Leu1873Val	missense_variant	Exon 26 of 44		NP_001278938.1	Q5T1H1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6 link	c.5617C>G	p.Leu1873Val	missense_variant	Exon 26 of 43	5	NM_001142800.2	ENSP00000424243.1		Q5T1H1-1
EYS	ENST00000370621.7 link	c.5617C>G	p.Leu1873Val	missense_variant	Exon 26 of 44	1		ENSP00000359655.3		Q5T1H1-3

Frequencies

GnomAD3 genomes

AF:

0.0985

AC:

14972

AN:

152066

Hom.:

916

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0280

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.0723

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0736

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.0967

GnomAD3 exomes

AF:

0.118

AC:

17874

AN:

151430

Hom.:

1211

AF XY:

0.119

AC XY:

9555

AN XY:

80350

show subpopulations

Gnomad AFR exome

AF:

0.0222

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.0822

Gnomad EAS exome

AF:

0.175

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0820

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.132

AC:

184174

AN:

1395658

Hom.:

12861

Cov.:

AF XY:

0.132

AC XY:

90609

AN XY:

688162

show subpopulations

Gnomad4 AFR exome

AF:

0.0200

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.0797

Gnomad4 EAS exome

AF:

0.145

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0808

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.0983

AC:

14966

AN:

152184

Hom.:

913

Cov.:

AF XY:

0.0967

AC XY:

7190

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0279

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.0723

Gnomad4 EAS

AF:

0.166

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.0736

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.0957

Alfa

AF:

0.126

Hom.:

1015

Bravo

AF:

0.102

TwinsUK

AF:

0.135

AC:

499

ALSPAC

AF:

0.128

AC:

494

ESP6500AA

AF:

0.0282

AC:

ESP6500EA

AF:

0.140

AC:

445

ExAC

AF:

0.0948

AC:

2078

Asia WGS

AF:

0.121

AC:

421

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Sep 25, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 11, 2011

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Retinitis pigmentosa

Benign:2

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.1

DANN

Benign

0.24

DEOGEN2

Benign

0.035

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.32

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.088

Sift

Benign

0.61

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0010

B;B

Vest4

0.021

MPC

0.0097

ClinPred

0.00026

GERP RS

2.0

Varity_R

0.040

gMVP

0.0094

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