rs9353806

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142800.2(EYS):c.5705A>T(p.Asn1902Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,521,466 control chromosomes in the GnomAD database, including 67,207 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 5939 hom., cov: 32)

Exomes 𝑓: 0.30 ( 61268 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.304

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011012852).

BP6

Variant 6-64439292-T-A is Benign according to our data. Variant chr6-64439292-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 137256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-64439292-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2 linkuse as main transcript	c.5705A>T	p.Asn1902Ile	missense_variant	27/43	ENST00000503581.6
EYS	NM_001292009.2 linkuse as main transcript	c.5705A>T	p.Asn1902Ile	missense_variant	27/44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6 linkuse as main transcript	c.5705A>T	p.Asn1902Ile	missense_variant	27/43	5	NM_001142800.2	A2	Q5T1H1-1
EYS	ENST00000370621.7 linkuse as main transcript	c.5705A>T	p.Asn1902Ile	missense_variant	27/44	1		P2	Q5T1H1-3

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

41968

AN:

151456

Hom.:

5936

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.465

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.296

GnomAD3 exomes

AF:

0.305

AC:

39820

AN:

130680

Hom.:

6254

AF XY:

0.305

AC XY:

21283

AN XY:

69714

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.286

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.490

Gnomad SAS exome

AF:

0.290

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.289

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

AF:

0.296

AC:

406032

AN:

1369892

Hom.:

61268

Cov.:

AF XY:

0.297

AC XY:

200056

AN XY:

674654

show subpopulations

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.286

Gnomad4 ASJ exome

AF:

0.286

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.347

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.302

GnomAD4 genome

AF:

0.277

AC:

41992

AN:

151574

Hom.:

5939

Cov.:

AF XY:

0.281

AC XY:

20780

AN XY:

74058

show subpopulations

Gnomad4 AFR

AF:

0.207

Gnomad4 AMR

AF:

0.284

Gnomad4 ASJ

AF:

0.275

Gnomad4 EAS

AF:

0.465

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.348

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.280

Hom.:

4605

Bravo

AF:

0.275

TwinsUK

AF:

0.302

AC:

1120

ALSPAC

AF:

0.289

AC:

1115

ExAC

AF:

0.274

AC:

5743

Asia WGS

AF:

0.347

AC:

1207

AN:

3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2011	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 17, 2023	- -

Retinitis pigmentosa 25

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

Retinitis pigmentosa

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.52

T;T

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.85

P;P

Vest4

0.27

MPC

0.018

ClinPred

0.019

GERP RS

-1.4

Varity_R

0.17

gMVP

0.034

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over