rs17411795

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142800.2(EYS):c.1922A>T(p.Glu641Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,551,002 control chromosomes in the GnomAD database, including 31,981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. E641E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.16 ( 2384 hom., cov: 33)

Exomes 𝑓: 0.20 ( 29597 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.425

Publications

21 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004574895).

BP6

Variant 6-65295964-T-A is Benign according to our data. Variant chr6-65295964-T-A is described in ClinVar as Benign. ClinVar VariationId is 137268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.1922A>T	p.Glu641Val	missense_variant	Exon 12 of 43	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2 link	c.1922A>T	p.Glu641Val	missense_variant	Exon 12 of 44		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
EYS	ENST00000503581.6 link	c.1922A>T	p.Glu641Val	missense_variant	Exon 12 of 43	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7 link	c.1922A>T	p.Glu641Val	missense_variant	Exon 12 of 44	1		ENSP00000359655.3
EYS	ENST00000370615.3 link	n.360A>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
EYS	ENST00000447127.1 link	n.378A>T		non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24611

AN:

151796

Hom.:

2385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0749

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.0583

Gnomad SAS

AF:

0.0884

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.142

GnomAD2 exomes

AF:

0.168

AC:

26497

AN:

157354

AF XY:

0.165

show subpopulations

Gnomad AFR exome

AF:

0.0660

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.207

Gnomad EAS exome

AF:

0.0483

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.215

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.200

AC:

279555

AN:

1399088

Hom.:

29597

Cov.:

AF XY:

0.197

AC XY:

135724

AN XY:

690048

show subpopulations

African (AFR)

AF:

0.0662

AC:

2091

AN:

31580

American (AMR)

AF:

0.123

AC:

4402

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

5303

AN:

25158

East Asian (EAS)

AF:

0.0739

AC:

2642

AN:

35728

South Asian (SAS)

AF:

0.0889

AC:

7046

AN:

79218

European-Finnish (FIN)

AF:

0.281

AC:

13859

AN:

49364

Middle Eastern (MID)

AF:

0.142

AC:

809

AN:

5700

European-Non Finnish (NFE)

AF:

0.216

AC:

232876

AN:

1078594

Other (OTH)

AF:

0.181

AC:

10527

AN:

58042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

13550

27101

40651

54202

67752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7972

15944

23916

31888

39860

<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:

0.162

AC:

24611

AN:

151914

Hom.:

2384

Cov.:

AF XY:

0.161

AC XY:

11970

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.0748

AC:

3102

AN:

41476

American (AMR)

AF:

0.134

AC:

2036

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

683

AN:

3470

East Asian (EAS)

AF:

0.0581

AC:

300

AN:

5164

South Asian (SAS)

AF:

0.0885

AC:

427

AN:

4826

European-Finnish (FIN)

AF:

0.276

AC:

2919

AN:

10562

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14694

AN:

67864

Other (OTH)

AF:

0.140

AC:

295

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1030

2060

3090

4120

5150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.202

Hom.:

2403

Bravo

AF:

0.148

TwinsUK

AF:

0.217

AC:

806

ALSPAC

AF:

0.215

AC:

829

ESP6500AA

AF:

0.0824

AC:

114

ESP6500EA

AF:

0.209

AC:

666

ExAC

AF:

0.153

AC:

3841

Asia WGS

AF:

0.0750

AC:

262

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 03, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

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. -

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 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

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.48

MutationAssessor

Pathogenic

3.4

M;M

PhyloP100

0.42

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-4.4

D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0060

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.97

D;.

Vest4

0.30

MPC

0.057

ClinPred

0.053

GERP RS

0.45

Varity_R

0.20

gMVP

0.77

Mutation Taster

=91/9

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