rs17404123

Positions:

chr6-64593207-T-C

Variant summary

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

The NM_001142800.2(EYS):c.3787A>G(p.Ile1263Val) 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 1,549,136 control chromosomes in the GnomAD database, including 13,834 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 (★★). Synonymous variant affecting the same amino acid position (i.e. I1263I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.10 ( 927 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12907 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0780

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=0.0046322346).

BP6

Variant 6-64593207-T-C is Benign according to our data. Variant chr6-64593207-T-C is described in ClinVar as [Benign]. Clinvar id is 137241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-64593207-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2 linkuse as main transcript	c.3787A>G	p.Ile1263Val	missense_variant	25/43	ENST00000503581.6
EYS	NM_001292009.2 linkuse as main transcript	c.3787A>G	p.Ile1263Val	missense_variant	25/44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6 linkuse as main transcript	c.3787A>G	p.Ile1263Val	missense_variant	25/43	5	NM_001142800.2	A2	Q5T1H1-1
EYS	ENST00000370621.7 linkuse as main transcript	c.3787A>G	p.Ile1263Val	missense_variant	25/44	1		P2	Q5T1H1-3
EYS	ENST00000330816.5 linkuse as main transcript	n.408A>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15349

AN:

151970

Hom.:

930

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0365

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0721

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0739

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.0986

GnomAD3 exomes

AF:

0.118

AC:

18260

AN:

154972

Hom.:

1244

AF XY:

0.118

AC XY:

9739

AN XY:

82202

show subpopulations

Gnomad AFR exome

AF:

0.0304

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.0818

Gnomad EAS exome

AF:

0.175

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0814

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.132

AC:

184867

AN:

1397048

Hom.:

12907

Cov.:

AF XY:

0.132

AC XY:

90903

AN XY:

688982

show subpopulations

Gnomad4 AFR exome

AF:

0.0303

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.0797

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0808

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.101

AC:

15344

AN:

152088

Hom.:

927

Cov.:

AF XY:

0.0992

AC XY:

7375

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0364

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.0721

Gnomad4 EAS

AF:

0.166

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.0739

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.0975

Alfa

AF:

0.127

Hom.:

1977

Bravo

AF:

0.105

TwinsUK

AF:

0.135

AC:

499

ALSPAC

AF:

0.127

AC:

490

ESP6500AA

AF:

0.0354

AC:

ESP6500EA

AF:

0.140

AC:

446

ExAC

AF:

0.0944

AC:

2295

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:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 11, 2011	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Retinitis pigmentosa

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Retinitis pigmentosa 25

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.062

DANN

Benign

0.16

DEOGEN2

Benign

0.023

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00065

LIST_S2

Benign

0.15

T;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.55

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.22

PROVEAN

Benign

0.12

N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.020

MPC

0.0099

ClinPred

0.00026

GERP RS

0.77

Varity_R

0.019

gMVP

0.060

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