rs624851

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.4256T>C(p.Leu1419Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 1,550,802 control chromosomes in the GnomAD database, including 402,452 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.

Frequency

Genomes: 𝑓 0.77 ( 45597 hom., cov: 30)

Exomes 𝑓: 0.71 ( 356855 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.05

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=8.1337487E-7).

BP6

Variant 6-64591611-A-G is Benign according to our data. Variant chr6-64591611-A-G is described in ClinVar as Benign. ClinVar VariationId is 93611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 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.4256T>C	p.Leu1419Ser	missense	Exon 26 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.4256T>C	p.Leu1419Ser	missense	Exon 26 of 44	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.4256T>C	p.Leu1419Ser	missense	Exon 26 of 43	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.4256T>C	p.Leu1419Ser	missense	Exon 26 of 44	ENSP00000359655.3	Q5T1H1-3

Frequencies

GnomAD3 genomes

AF:

0.767

AC:

116364

AN:

151782

Hom.:

45533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.942

Gnomad AMI

AF:

0.653

Gnomad AMR

AF:

0.745

Gnomad ASJ

AF:

0.650

Gnomad EAS

AF:

0.666

Gnomad SAS

AF:

0.772

Gnomad FIN

AF:

0.702

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.711

GnomAD2 exomes

AF:

0.729

AC:

111796

AN:

153440

AF XY:

0.728

show subpopulations

Gnomad AFR exome

AF:

0.950

Gnomad AMR exome

AF:

0.777

Gnomad ASJ exome

AF:

0.642

Gnomad EAS exome

AF:

0.659

Gnomad FIN exome

AF:

0.704

Gnomad NFE exome

AF:

0.692

Gnomad OTH exome

AF:

0.712

GnomAD4 exome

AF:

0.713

AC:

996812

AN:

1398902

Hom.:

356855

Cov.:

AF XY:

0.713

AC XY:

492035

AN XY:

689970

show subpopulations

African (AFR)

AF:

0.948

AC:

29938

AN:

31582

American (AMR)

AF:

0.775

AC:

27681

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.648

AC:

16300

AN:

25158

East Asian (EAS)

AF:

0.699

AC:

24990

AN:

35734

South Asian (SAS)

AF:

0.778

AC:

61620

AN:

79224

European-Finnish (FIN)

AF:

0.709

AC:

34945

AN:

49266

Middle Eastern (MID)

AF:

0.635

AC:

3616

AN:

5698

European-Non Finnish (NFE)

AF:

0.701

AC:

756282

AN:

1078554

Other (OTH)

AF:

0.715

AC:

41440

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16413

32826

49240

65653

82066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19448

38896

58344

77792

97240

<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:

0.767

AC:

116486

AN:

151900

Hom.:

45597

Cov.:

AF XY:

0.766

AC XY:

56826

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.942

AC:

39070

AN:

41480

American (AMR)

AF:

0.745

AC:

11339

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.650

AC:

2255

AN:

3468

East Asian (EAS)

AF:

0.666

AC:

3417

AN:

5134

South Asian (SAS)

AF:

0.772

AC:

3718

AN:

4816

European-Finnish (FIN)

AF:

0.702

AC:

7407

AN:

10552

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.692

AC:

47001

AN:

67930

Other (OTH)

AF:

0.714

AC:

1503

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1297

2593

3890

5186

6483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.712

Hom.:

124682

Bravo

AF:

0.777

TwinsUK

AF:

0.697

AC:

2586

ALSPAC

AF:

0.708

AC:

2728

ESP6500AA

AF:

0.942

AC:

1304

ESP6500EA

AF:

0.701

AC:

2232

ExAC

AF:

0.737

AC:

15406

Asia WGS

AF:

0.745

AC:

2590

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

0.087

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.1

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.040

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.19

MetaRNN

Benign

8.1e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

0.12

REVEL

Benign

0.25

Sift

Benign

0.034

Sift4G

Benign

0.32

Polyphen

0.010

Vest4

0.029

MPC

0.0094

ClinPred

0.0043

GERP RS

0.38

Varity_R

0.037

gMVP

0.045

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

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