rs9345601

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001142800.2(EYS):c.1809C>T(p.Val603Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,548,970 control chromosomes in the GnomAD database, including 271,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 22770 hom., cov: 33)

Exomes 𝑓: 0.59 ( 248609 hom. )

Consequence

EYS
NM_001142800.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 1.55

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-65296077-G-A is Benign according to our data. Variant chr6-65296077-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 137266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-65296077-G-A is described in Lovd as [Benign]. Variant chr6-65296077-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.1809C>T	p.Val603Val	synonymous_variant	Exon 12 of 43	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.1809C>T	p.Val603Val	synonymous_variant	Exon 12 of 44		NP_001278938.1	Q5T1H1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EYS	ENST00000503581.6 link	c.1809C>T	p.Val603Val	synonymous_variant	Exon 12 of 43	5	NM_001142800.2	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7 link	c.1809C>T	p.Val603Val	synonymous_variant	Exon 12 of 44	1		ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000370615.3 link	n.247C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
EYS	ENST00000447127.1 link	n.265C>T		non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

78928

AN:

151654

Hom.:

22755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.735

Gnomad AMR

AF:

0.667

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.581

GnomAD3 exomes

AF:

0.625

AC:

97415

AN:

155874

Hom.:

31999

AF XY:

0.625

AC XY:

51566

AN XY:

82540

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.763

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.917

Gnomad SAS exome

AF:

0.659

Gnomad FIN exome

AF:

0.567

Gnomad NFE exome

AF:

0.584

Gnomad OTH exome

AF:

0.596

GnomAD4 exome

AF:

0.591

AC:

825266

AN:

1397196

Hom.:

248609

Cov.:

AF XY:

0.593

AC XY:

408843

AN XY:

689088

show subpopulations

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.745

Gnomad4 ASJ exome

AF:

0.521

Gnomad4 EAS exome

AF:

0.908

Gnomad4 SAS exome

AF:

0.660

Gnomad4 FIN exome

AF:

0.563

Gnomad4 NFE exome

AF:

0.583

Gnomad4 OTH exome

AF:

0.588

GnomAD4 genome

AF:

0.520

AC:

78964

AN:

151774

Hom.:

22770

Cov.:

AF XY:

0.527

AC XY:

39100

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.275

Gnomad4 AMR

AF:

0.668

Gnomad4 ASJ

AF:

0.524

Gnomad4 EAS

AF:

0.906

Gnomad4 SAS

AF:

0.681

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.586

Alfa

AF:

0.561

Hom.:

9059

Bravo

AF:

0.520

Asia WGS

AF:

0.761

AC:

2640

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Apr 17, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

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

- -

Jul 05, 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. -

Mar 17, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 25

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 28, 2017

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

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. -

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

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.0

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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