dbSNP rs12662610: EYS:p.Thr1312Thr (chr6-64591931-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001142800.2(EYS):c.3936A>G(p.Thr1312Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,532,292 control chromosomes in the GnomAD database, including 13,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 946 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12650 hom. )

Consequence

EYS
NM_001142800.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.00400

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-64591931-T-C is Benign according to our data. Variant chr6-64591931-T-C is described in ClinVar as [Benign]. Clinvar id is 93607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-64591931-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.004 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.3936A>G	p.Thr1312Thr	synonymous_variant	Exon 26 of 43	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.3936A>G	p.Thr1312Thr	synonymous_variant	Exon 26 of 44		NP_001278938.1	Q5T1H1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6 link	c.3936A>G	p.Thr1312Thr	synonymous_variant	Exon 26 of 43	5	NM_001142800.2	ENSP00000424243.1		Q5T1H1-1
EYS	ENST00000370621.7 link	c.3936A>G	p.Thr1312Thr	synonymous_variant	Exon 26 of 44	1		ENSP00000359655.3		Q5T1H1-3

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15754

AN:

152028

Hom.:

946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0458

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0723

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.0738

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.114

AC:

16802

AN:

147292

Hom.:

1099

AF XY:

0.115

AC XY:

8955

AN XY:

78090

show subpopulations

Gnomad AFR exome

AF:

0.0393

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.0769

Gnomad EAS exome

AF:

0.171

Gnomad SAS exome

AF:

0.0975

Gnomad FIN exome

AF:

0.0794

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.130

AC:

179718

AN:

1380146

Hom.:

12650

Cov.:

AF XY:

0.130

AC XY:

88117

AN XY:

678948

show subpopulations

Gnomad4 AFR exome

AF:

0.0394

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.0772

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0798

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.104

AC:

15763

AN:

152146

Hom.:

946

Cov.:

AF XY:

0.102

AC XY:

7582

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0460

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.0723

Gnomad4 EAS

AF:

0.165

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.0738

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.0999

Alfa

AF:

0.117

Hom.:

454

Bravo

AF:

0.108

Asia WGS

AF:

0.124

AC:

431

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 19, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 11, 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. -

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

- -

Retinitis pigmentosa 25

Benign:1

Jul 01, 2021

Genome-Nilou Lab

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

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.59

DANN

Benign

0.28

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

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