rs61753610

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.1712A>G(p.Gln571Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,611,088 control chromosomes in the GnomAD database, including 22,985 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1533 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21452 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.65

Publications

22 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=8.687973E-4).

BP6

Variant 6-65335034-T-C is Benign according to our data. Variant chr6-65335034-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EYS	NM_001142800.2	MANE Select	c.1712A>G	p.Gln571Arg	missense	Exon 11 of 43	NP_001136272.1
EYS	NM_001292009.2		c.1712A>G	p.Gln571Arg	missense	Exon 11 of 44	NP_001278938.1
EYS	NM_001142801.2		c.1712A>G	p.Gln571Arg	missense	Exon 11 of 12	NP_001136273.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EYS	ENST00000503581.6	TSL:5 MANE Select	c.1712A>G	p.Gln571Arg	missense	Exon 11 of 43	ENSP00000424243.1
EYS	ENST00000370621.7	TSL:1	c.1712A>G	p.Gln571Arg	missense	Exon 11 of 44	ENSP00000359655.3
EYS	ENST00000393380.6	TSL:1	c.1712A>G	p.Gln571Arg	missense	Exon 11 of 12	ENSP00000377042.2

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20050

AN:

151684

Hom.:

1530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0337

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.131

GnomAD2 exomes

AF:

0.159

AC:

39776

AN:

250118

AF XY:

0.162

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.180

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.168

AC:

244783

AN:

1459286

Hom.:

21452

Cov.:

AF XY:

0.168

AC XY:

122279

AN XY:

726080

show subpopulations

African (AFR)

AF:

0.0267

AC:

890

AN:

33376

American (AMR)

AF:

0.168

AC:

7479

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

3587

AN:

26058

East Asian (EAS)

AF:

0.116

AC:

4593

AN:

39642

South Asian (SAS)

AF:

0.174

AC:

14981

AN:

86208

European-Finnish (FIN)

AF:

0.177

AC:

9382

AN:

53138

Middle Eastern (MID)

AF:

0.136

AC:

783

AN:

5748

European-Non Finnish (NFE)

AF:

0.174

AC:

193645

AN:

1110312

Other (OTH)

AF:

0.157

AC:

9443

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

10737

21474

32210

42947

53684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6728

13456

20184

26912

33640

<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:

0.132

AC:

20055

AN:

151802

Hom.:

1533

Cov.:

AF XY:

0.133

AC XY:

9831

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.0336

AC:

1394

AN:

41516

American (AMR)

AF:

0.167

AC:

2527

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

493

AN:

3464

East Asian (EAS)

AF:

0.109

AC:

559

AN:

5122

South Asian (SAS)

AF:

0.172

AC:

830

AN:

4824

European-Finnish (FIN)

AF:

0.182

AC:

1925

AN:

10600

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11777

AN:

67792

Other (OTH)

AF:

0.134

AC:

283

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

908

1816

2724

3632

4540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.156

Hom.:

4715

Bravo

AF:

0.125

TwinsUK

AF:

0.168

AC:

624

ALSPAC

AF:

0.173

AC:

667

ESP6500AA

AF:

0.0336

AC:

148

ESP6500EA

AF:

0.173

AC:

1485

ExAC

AF:

0.156

AC:

18983

Asia WGS

AF:

0.148

AC:

514

AN:

3478

EpiCase

AF:

0.176

EpiControl

AF:

0.180

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Retinitis pigmentosa 25 (3)

not provided (2)

Retinitis pigmentosa (2)

Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.5

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.023

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.43

MetaRNN

Benign

0.00087

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.63

PhyloP100

1.7

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.1

REVEL

Benign

0.033

Sift

Benign

0.40

Sift4G

Uncertain

0.0030

Polyphen

0.22

Vest4

0.19

MPC

0.0099

ClinPred

0.0048

GERP RS

2.2

Varity_R

0.061

gMVP

0.62

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

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