chr6-64590357-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001142800.2(EYS):c.5510G>C(p.Trp1837Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,551,246 control chromosomes in the GnomAD database, including 24 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 24 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:9

Conservation

PhyloP100: 0.444

Publications

4 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049631596).

BP6

Variant 6-64590357-C-G is Benign according to our data. Variant chr6-64590357-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 195937.

BS2

High Homozygotes in GnomAdExome4 at 24 AR,AD gene

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.5510G>C	p.Trp1837Ser	missense	Exon 26 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.5510G>C	p.Trp1837Ser	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.5510G>C	p.Trp1837Ser	missense	Exon 26 of 43	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.5510G>C	p.Trp1837Ser	missense	Exon 26 of 44	ENSP00000359655.3	Q5T1H1-3

Frequencies

GnomAD3 genomes

AF:

0.00326

AC:

496

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00444

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00399

AC:

614

AN:

153716

AF XY:

0.00397

show subpopulations

Gnomad AFR exome

AF:

0.000506

Gnomad AMR exome

AF:

0.00267

Gnomad ASJ exome

AF:

0.0266

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000262

Gnomad NFE exome

AF:

0.00497

Gnomad OTH exome

AF:

0.00370

GnomAD4 exome

AF:

0.00419

AC:

5869

AN:

1399056

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

2899

AN XY:

690034

show subpopulations

African (AFR)

AF:

0.000728

AC:

AN:

31578

American (AMR)

AF:

0.00294

AC:

105

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.0284

AC:

714

AN:

25156

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.000164

AC:

AN:

79232

European-Finnish (FIN)

AF:

0.000223

AC:

AN:

49276

Middle Eastern (MID)

AF:

0.00527

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00436

AC:

4707

AN:

1078694

Other (OTH)

AF:

0.00459

AC:

266

AN:

57986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

319

638

958

1277

1596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

376

564

752

940

<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:

0.00326

AC:

496

AN:

152190

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

221

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00104

AC:

AN:

41540

American (AMR)

AF:

0.00275

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00444

AC:

302

AN:

67988

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

113

141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00633

Hom.:

Bravo

AF:

0.00357

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00283

AC:

ExAC

AF:

0.00439

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Retinitis pigmentosa (3)

not specified (2)

Retinitis pigmentosa 25 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.040

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0050

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.0

PhyloP100

0.44

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.75

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

Sift4G

Benign

0.39

Polyphen

0.98

Vest4

0.34

MVP

0.55

MPC

0.057

ClinPred

0.057

GERP RS

3.3

Varity_R

0.20

gMVP

0.032

Mutation Taster

=96/4

polymorphism

(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