rs9342464

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.1891G>A(p.Gly631Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,550,630 control chromosomes in the GnomAD database, including 271,627 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 (★★). Synonymous variant affecting the same amino acid position (i.e. G631G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.52 ( 22765 hom., cov: 32)

Exomes 𝑓: 0.59 ( 248862 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.90

Publications

30 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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=1.4348618E-6).

BP6

Variant 6-65295995-C-T is Benign according to our data. Variant chr6-65295995-C-T is described in ClinVar as Benign. ClinVar VariationId is 137267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.1891G>A	p.Gly631Ser	missense	Exon 12 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.1891G>A	p.Gly631Ser	missense	Exon 12 of 44	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EYS	ENST00000503581.6	TSL:5 MANE Select	c.1891G>A	p.Gly631Ser	missense	Exon 12 of 43	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7	TSL:1	c.1891G>A	p.Gly631Ser	missense	Exon 12 of 44	ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000370615.3	TSL:3	n.329G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

78876

AN:

151592

Hom.:

22751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.735

Gnomad AMR

AF:

0.668

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.580

GnomAD2 exomes

AF:

0.625

AC:

98325

AN:

157416

AF XY:

0.625

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.763

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.917

Gnomad FIN exome

AF:

0.566

Gnomad NFE exome

AF:

0.584

Gnomad OTH exome

AF:

0.595

GnomAD4 exome

AF:

0.591

AC:

826335

AN:

1398920

Hom.:

248862

Cov.:

AF XY:

0.593

AC XY:

409393

AN XY:

689948

show subpopulations

African (AFR)

AF:

0.266

AC:

8392

AN:

31578

American (AMR)

AF:

0.745

AC:

26598

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

13102

AN:

25152

East Asian (EAS)

AF:

0.908

AC:

32450

AN:

35730

South Asian (SAS)

AF:

0.660

AC:

52287

AN:

79190

European-Finnish (FIN)

AF:

0.563

AC:

27778

AN:

49378

Middle Eastern (MID)

AF:

0.542

AC:

3088

AN:

5698

European-Non Finnish (NFE)

AF:

0.583

AC:

628516

AN:

1078456

Other (OTH)

AF:

0.588

AC:

34124

AN:

58040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

18082

36165

54247

72330

90412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17554

35108

52662

70216

87770

<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:

0.520

AC:

78910

AN:

151710

Hom.:

22765

Cov.:

AF XY:

0.527

AC XY:

39084

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.274

AC:

11345

AN:

41396

American (AMR)

AF:

0.668

AC:

10159

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1817

AN:

3466

East Asian (EAS)

AF:

0.906

AC:

4655

AN:

5140

South Asian (SAS)

AF:

0.681

AC:

3285

AN:

4824

European-Finnish (FIN)

AF:

0.571

AC:

6017

AN:

10540

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.583

AC:

39568

AN:

67818

Other (OTH)

AF:

0.586

AC:

1236

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1715

3430

5144

6859

8574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.574

Hom.:

82765

Bravo

AF:

0.520

TwinsUK

AF:

0.578

AC:

2142

ALSPAC

AF:

0.581

AC:

2239

ESP6500AA

AF:

0.301

AC:

416

ESP6500EA

AF:

0.583

AC:

1856

ExAC

AF:

0.561

AC:

13919

Asia WGS

AF:

0.761

AC:

2641

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Retinitis pigmentosa 25 (4)

Retinitis pigmentosa (2)

not provided (1)

Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.1

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.024

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0000014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

1.9

PrimateAI

Benign

0.22

PROVEAN

Benign

1.1

REVEL

Benign

0.21

Sift

Benign

0.11

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.13

MPC

0.0097

ClinPred

0.0050

GERP RS

1.7

Varity_R

0.025

gMVP

0.72

Mutation Taster

=98/2

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

Computational scores

Splicing

Publications

Other links and lift over