rs9353806

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

3
15

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]

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 rank MANE Protein UniProt
EYSNM_001142800.2 linkc.5705A>T p.Asn1902Ile missense_variant Exon 27 of 43 ENST00000503581.6 NP_001136272.1 Q5T1H1-1
EYSNM_001292009.2 linkc.5705A>T p.Asn1902Ile missense_variant Exon 27 of 44 NP_001278938.1 Q5T1H1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EYSENST00000503581.6 linkc.5705A>T p.Asn1902Ile missense_variant Exon 27 of 43 5 NM_001142800.2 ENSP00000424243.1 Q5T1H1-1
EYSENST00000370621.7 linkc.5705A>T p.Asn1902Ile missense_variant Exon 27 of 44 1 ENSP00000359655.3 Q5T1H1-3

Frequencies

GnomAD3 genomes
AF:
0.277
AC:
41968
AN:
151456
Hom.:
5936
Cov.:
32
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.:
30
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.:
32
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
Apr 17, 2023
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jul 05, 2011
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Retinitis pigmentosa 25 Benign:2
Nov 29, 2023
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jul 01, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Retinitis pigmentosa Benign:2
Sep 16, 2020
Natera, Inc.
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

not provided Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Retinal dystrophy Benign:1
Oct 01, 2023
Dept Of Ophthalmology, Nagoya University
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.038
.;T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.65
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.52
T;T
MetaRNN
Benign
0.0011
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;N
PrimateAI
Benign
0.40
T
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
T
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.

Other links and lift over

dbSNP: rs9353806; hg19: chr6-65149185; COSMIC: COSV65467257; API