rs17404123

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_001142800.2(EYS):c.3787A>G(p.Ile1263Val) 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 1,549,136 control chromosomes in the GnomAD database, including 13,834 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. I1263I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.10 ( 927 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12907 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0780

Publications

16 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=0.0046322346).

BP6

Variant 6-64593207-T-C is Benign according to our data. Variant chr6-64593207-T-C is described in ClinVar as Benign. ClinVar VariationId is 137241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. 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.3787A>G	p.Ile1263Val	missense	Exon 25 of 43	NP_001136272.1
	EYS	NM_001292009.2		c.3787A>G	p.Ile1263Val	missense	Exon 25 of 44	NP_001278938.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EYS	ENST00000503581.6	TSL:5 MANE Select	c.3787A>G	p.Ile1263Val	missense	Exon 25 of 43	ENSP00000424243.1
EYS	ENST00000370621.7	TSL:1	c.3787A>G	p.Ile1263Val	missense	Exon 25 of 44	ENSP00000359655.3
EYS	ENST00000330816.5	TSL:3	n.408A>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15349

AN:

151970

Hom.:

930

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0365

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0721

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0739

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.0986

GnomAD2 exomes

AF:

0.118

AC:

18260

AN:

154972

AF XY:

0.118

show subpopulations

Gnomad AFR exome

AF:

0.0304

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.0818

Gnomad EAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.0814

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.132

AC:

184867

AN:

1397048

Hom.:

12907

Cov.:

AF XY:

0.132

AC XY:

90903

AN XY:

688982

show subpopulations

African (AFR)

AF:

0.0303

AC:

952

AN:

31448

American (AMR)

AF:

0.135

AC:

4782

AN:

35412

Ashkenazi Jewish (ASJ)

AF:

0.0797

AC:

2004

AN:

25140

East Asian (EAS)

AF:

0.144

AC:

5137

AN:

35554

South Asian (SAS)

AF:

0.104

AC:

8239

AN:

78884

European-Finnish (FIN)

AF:

0.0808

AC:

3980

AN:

49264

Middle Eastern (MID)

AF:

0.0571

AC:

325

AN:

5688

European-Non Finnish (NFE)

AF:

0.141

AC:

152255

AN:

1077742

Other (OTH)

AF:

0.124

AC:

7193

AN:

57916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

7725

15450

23176

30901

38626

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:

15344

AN:

152088

Hom.:

927

Cov.:

AF XY:

0.0992

AC XY:

7375

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0364

AC:

1512

AN:

41524

American (AMR)

AF:

0.125

AC:

1903

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0721

AC:

250

AN:

3466

East Asian (EAS)

AF:

0.166

AC:

853

AN:

5142

South Asian (SAS)

AF:

0.113

AC:

543

AN:

4818

European-Finnish (FIN)

AF:

0.0739

AC:

783

AN:

10596

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9178

AN:

67952

Other (OTH)

AF:

0.0975

AC:

206

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

681

1362

2043

2724

3405

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:

0.122

Hom.:

2755

Bravo

AF:

0.105

TwinsUK

AF:

0.135

AC:

499

ALSPAC

AF:

0.127

AC:

490

ESP6500AA

AF:

0.0354

AC:

ESP6500EA

AF:

0.140

AC:

446

ExAC

AF:

0.0944

AC:

2295

Asia WGS

AF:

0.121

AC:

421

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)

Retinitis pigmentosa (2)

not provided (1)

Retinal dystrophy (1)

Retinitis pigmentosa 25 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.062

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.023

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00065

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.55

PhyloP100

-0.078

PrimateAI

Benign

0.22

PROVEAN

Benign

0.12

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.020

MPC

0.0099

ClinPred

0.00026

GERP RS

0.77

Varity_R

0.019

gMVP

0.060

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over