chr6-65295995-C-T

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.1891G>A(p.Gly631Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,550,630 control chromosomes in the GnomAD database, including 271,627 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 0.52 ( 22765 hom., cov: 32)

Exomes 𝑓: 0.59 ( 248862 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.90

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=1.4348618E-6).

BP6

Variant 6-65295995-C-T is Benign according to our data. Variant chr6-65295995-C-T is described in ClinVar as [Benign]. Clinvar id is 137267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-65295995-C-T is described in Lovd as [Benign].

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.1891G>A	p.Gly631Ser	missense_variant	Exon 12 of 43	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.1891G>A	p.Gly631Ser	missense_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.1891G>A	p.Gly631Ser	missense_variant	Exon 12 of 43	5	NM_001142800.2	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7 link	c.1891G>A	p.Gly631Ser	missense_variant	Exon 12 of 44	1		ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000370615.3 link	n.329G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3
EYS	ENST00000447127.1 link	n.347G>A		non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

78876

AN:

151592

Hom.:

22751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.735

Gnomad AMR

AF:

0.668

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.580

GnomAD3 exomes

AF:

0.625

AC:

98325

AN:

157416

Hom.:

32264

AF XY:

0.625

AC XY:

51904

AN XY:

83060

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.763

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.917

Gnomad SAS exome

AF:

0.660

Gnomad FIN exome

AF:

0.566

Gnomad NFE exome

AF:

0.584

Gnomad OTH exome

AF:

0.595

GnomAD4 exome

AF:

0.591

AC:

826335

AN:

1398920

Hom.:

248862

Cov.:

AF XY:

0.593

AC XY:

409393

AN XY:

689948

show subpopulations

Gnomad4 AFR exome

AF:

0.266

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:

78910

AN:

151710

Hom.:

22765

Cov.:

AF XY:

0.527

AC XY:

39084

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.274

Gnomad4 AMR

AF:

0.668

Gnomad4 ASJ

AF:

0.524

Gnomad4 EAS

AF:

0.906

Gnomad4 SAS

AF:

0.681

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.586

Alfa

AF:

0.585

Hom.:

40544

Bravo

AF:

0.520

TwinsUK

AF:

0.578

AC:

2142

ALSPAC

AF:

0.581

AC:

2239

ESP6500AA

AF:

0.301

AC:

416

ESP6500EA

AF:

0.583

AC:

1856

ExAC

AF:

0.561

AC:

13919

Asia WGS

AF:

0.761

AC:

2641

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

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

- -

Retinitis pigmentosa 25

Benign:4

Mar 04, 2015

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

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

- -

Jul 01, 2021

Genome-Nilou Lab

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 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. -

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

0.067

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.1

DANN

Benign

0.60

DEOGEN2

Benign

0.024

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0000014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.21

Sift

Benign

0.11

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0

B;.

Vest4

0.13

MPC

0.0097

ClinPred

0.0050

GERP RS

1.7

Varity_R

0.025

gMVP

0.72

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