rs62415827

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001292009.2(EYS):c.4543C>T(p.Arg1515Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,550,706 control chromosomes in the GnomAD database, including 13,830 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1515Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.10 ( 915 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12915 hom. )

Consequence

EYS
NM_001292009.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.352

Publications

14 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=0.001745969).

BP6

Variant 6-64591324-G-A is Benign according to our data. Variant chr6-64591324-G-A is described in ClinVar as Benign. ClinVar VariationId is 93613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292009.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.4543C>T	p.Arg1515Trp	missense	Exon 26 of 43	NP_001136272.1
	EYS	NM_001292009.2		c.4543C>T	p.Arg1515Trp	missense	Exon 26 of 44	NP_001278938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.4543C>T	p.Arg1515Trp	missense	Exon 26 of 43	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.4543C>T	p.Arg1515Trp	missense	Exon 26 of 44	ENSP00000359655.3

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15329

AN:

151862

Hom.:

918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0365

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0722

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0738

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.0985

GnomAD2 exomes

AF:

0.119

AC:

18262

AN:

153778

AF XY:

0.119

show subpopulations

Gnomad AFR exome

AF:

0.0305

Gnomad AMR exome

AF:

0.137

Gnomad ASJ exome

AF:

0.0821

Gnomad EAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.0819

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.132

AC:

185042

AN:

1398726

Hom.:

12915

Cov.:

AF XY:

0.132

AC XY:

91020

AN XY:

689906

show subpopulations

African (AFR)

AF:

0.0303

AC:

957

AN:

31582

American (AMR)

AF:

0.136

AC:

4840

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.0796

AC:

2004

AN:

25168

East Asian (EAS)

AF:

0.145

AC:

5169

AN:

35730

South Asian (SAS)

AF:

0.105

AC:

8286

AN:

79226

European-Finnish (FIN)

AF:

0.0808

AC:

3979

AN:

49268

Middle Eastern (MID)

AF:

0.0574

AC:

327

AN:

5696

European-Non Finnish (NFE)

AF:

0.141

AC:

152271

AN:

1078378

Other (OTH)

AF:

0.124

AC:

7209

AN:

57974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

9357

18714

28072

37429

46786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5576

11152

16728

22304

27880

<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:

15324

AN:

151980

Hom.:

915

Cov.:

AF XY:

0.0992

AC XY:

7371

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0364

AC:

1513

AN:

41516

American (AMR)

AF:

0.124

AC:

1893

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.0722

AC:

250

AN:

3464

East Asian (EAS)

AF:

0.165

AC:

849

AN:

5140

South Asian (SAS)

AF:

0.112

AC:

540

AN:

4814

European-Finnish (FIN)

AF:

0.0738

AC:

781

AN:

10582

Middle Eastern (MID)

AF:

0.0685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.135

AC:

9180

AN:

67944

Other (OTH)

AF:

0.0974

AC:

205

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

702

1404

2107

2809

3511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.121

Hom.:

2441

Bravo

AF:

0.105

TwinsUK

AF:

0.133

AC:

495

ALSPAC

AF:

0.127

AC:

489

ESP6500AA

AF:

0.0354

AC:

ESP6500EA

AF:

0.140

AC:

446

ExAC

AF:

0.0969

AC:

2109

Asia WGS

AF:

0.122

AC:

423

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Retinitis pigmentosa (2)

Retinal dystrophy (1)

Retinitis pigmentosa 25 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.55

PhyloP100

0.35

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.82

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.17

MPC

0.015

ClinPred

0.019

GERP RS

0.078

Varity_R

0.083

gMVP

0.14

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over