rs12663619

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001142800.2(EYS):c.4026C>T(p.Ser1342Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,550,060 control chromosomes in the GnomAD database, including 13,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 925 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12922 hom. )

Consequence

EYS
NM_001142800.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.0510

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

EYS-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
retinitis pigmentosa 25
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

EYS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 6-64591841-G-A is Benign according to our data. Variant chr6-64591841-G-A is described in ClinVar as Benign. ClinVar VariationId is 93609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.051 with no splicing effect.

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.4026C>T	p.Ser1342Ser	synonymous_variant	Exon 26 of 43	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2 link	c.4026C>T	p.Ser1342Ser	synonymous_variant	Exon 26 of 44		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6 link	c.4026C>T	p.Ser1342Ser	synonymous_variant	Exon 26 of 43	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7 link	c.4026C>T	p.Ser1342Ser	synonymous_variant	Exon 26 of 44	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15356

AN:

151962

Hom.:

928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0724

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0738

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.0991

GnomAD2 exomes

AF:

0.118

AC:

18146

AN:

153270

AF XY:

0.119

show subpopulations

Gnomad AFR exome

AF:

0.0304

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.0818

Gnomad EAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.0815

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.132

AC:

184760

AN:

1397980

Hom.:

12922

Cov.:

AF XY:

0.132

AC XY:

90885

AN XY:

689532

show subpopulations

African (AFR)

AF:

0.0302

AC:

953

AN:

31568

American (AMR)

AF:

0.135

AC:

4805

AN:

35648

Ashkenazi Jewish (ASJ)

AF:

0.0795

AC:

2000

AN:

25150

East Asian (EAS)

AF:

0.145

AC:

5169

AN:

35728

South Asian (SAS)

AF:

0.105

AC:

8288

AN:

79164

European-Finnish (FIN)

AF:

0.0807

AC:

3978

AN:

49266

Middle Eastern (MID)

AF:

0.0576

AC:

328

AN:

5696

European-Non Finnish (NFE)

AF:

0.141

AC:

152051

AN:

1077822

Other (OTH)

AF:

0.124

AC:

7188

AN:

57938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

9050

18100

27149

36199

45249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5562

11124

16686

22248

27810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.101

AC:

15351

AN:

152080

Hom.:

925

Cov.:

AF XY:

0.0994

AC XY:

7389

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0363

AC:

1507

AN:

41504

American (AMR)

AF:

0.125

AC:

1904

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.0724

AC:

251

AN:

3468

East Asian (EAS)

AF:

0.165

AC:

849

AN:

5144

South Asian (SAS)

AF:

0.113

AC:

544

AN:

4826

European-Finnish (FIN)

AF:

0.0738

AC:

783

AN:

10606

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9190

AN:

67964

Other (OTH)

AF:

0.0981

AC:

207

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

692

1384

2077

2769

3461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.117

Hom.:

620

Bravo

AF:

0.105

Asia WGS

AF:

0.122

AC:

423

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 19, 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. -

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

- -

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

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.5

(source)

DANN

Benign

0.63

PhyloP100

-0.051

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over