rs57312007

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.5244A>C(p.Leu1748Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,551,050 control chromosomes in the GnomAD database, including 12,752 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 921 hom., cov: 33)

Exomes 𝑓: 0.13 ( 11831 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.162

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=0.0030450225).

BP6

Variant 6-64590623-T-G is Benign according to our data. Variant chr6-64590623-T-G is described in ClinVar as [Benign]. Clinvar id is 93616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-64590623-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.5244A>C	p.Leu1748Phe	missense_variant	Exon 26 of 43	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.5244A>C	p.Leu1748Phe	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.5244A>C	p.Leu1748Phe	missense_variant	Exon 26 of 43	5	NM_001142800.2	ENSP00000424243.1		Q5T1H1-1
EYS	ENST00000370621.7 link	c.5244A>C	p.Leu1748Phe	missense_variant	Exon 26 of 44	1		ENSP00000359655.3		Q5T1H1-3

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15866

AN:

152094

Hom.:

922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0665

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0607

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.0203

Gnomad SAS

AF:

0.0909

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.0861

GnomAD3 exomes

AF:

0.102

AC:

15658

AN:

153662

Hom.:

1030

AF XY:

0.104

AC XY:

8484

AN XY:

81534

show subpopulations

Gnomad AFR exome

AF:

0.0647

Gnomad AMR exome

AF:

0.0471

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.0102

Gnomad SAS exome

AF:

0.0957

Gnomad FIN exome

AF:

0.175

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.126

AC:

175844

AN:

1398838

Hom.:

11831

Cov.:

AF XY:

0.125

AC XY:

86071

AN XY:

689922

show subpopulations

Gnomad4 AFR exome

AF:

0.0614

Gnomad4 AMR exome

AF:

0.0503

Gnomad4 ASJ exome

AF:

0.0999

Gnomad4 EAS exome

AF:

0.0400

Gnomad4 SAS exome

AF:

0.0961

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.104

AC:

15861

AN:

152212

Hom.:

921

Cov.:

AF XY:

0.104

AC XY:

7750

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0664

Gnomad4 AMR

AF:

0.0605

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.0203

Gnomad4 SAS

AF:

0.0902

Gnomad4 FIN

AF:

0.181

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.0857

Alfa

AF:

0.121

Hom.:

1866

Bravo

AF:

0.0929

TwinsUK

AF:

0.129

AC:

477

ALSPAC

AF:

0.141

AC:

542

ESP6500AA

AF:

0.0824

AC:

114

ESP6500EA

AF:

0.133

AC:

422

ExAC

AF:

0.0973

AC:

2065

Asia WGS

AF:

0.0540

AC:

188

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 20, 2011

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The variant is found in ARRP panel(s). -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa

Benign:2

Jan 13, 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. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:1

Oct 08, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 25

Benign:1

Jul 01, 2021

Genome-Nilou Lab

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

0.18

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.098

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.11

Sift

Benign

0.31

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.40

B;B

Vest4

0.023

MutPred

0.34

Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);

MPC

0.059

ClinPred

0.0044

GERP RS

-7.6

Varity_R

0.049

gMVP

0.0084

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