NM_001142800.2:c.1146T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001142800.2(EYS):c.1146T>C(p.Asn382Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,529,430 control chromosomes in the GnomAD database, including 201,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20917 hom., cov: 32)

Exomes 𝑓: 0.51 ( 180371 hom. )

Consequence

EYS
NM_001142800.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.00200

Publications

24 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-65402516-A-G is Benign according to our data. Variant chr6-65402516-A-G is described in ClinVar as Benign. ClinVar VariationId is 137262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.002 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.1146T>C	p.Asn382Asn	synonymous_variant	Exon 7 of 43	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.1146T>C	p.Asn382Asn	synonymous_variant	Exon 7 of 44		NP_001278938.1	Q5T1H1-3
EYS	NM_001142801.2 link	c.1146T>C	p.Asn382Asn	synonymous_variant	Exon 7 of 12		NP_001136273.1	Q5T1H1-4
EYS	NM_198283.2 link	c.1146T>C	p.Asn382Asn	synonymous_variant	Exon 6 of 10		NP_938024.1	Q5T1H1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EYS	ENST00000503581.6 link	c.1146T>C	p.Asn382Asn	synonymous_variant	Exon 7 of 43	5	NM_001142800.2	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7 link	c.1146T>C	p.Asn382Asn	synonymous_variant	Exon 7 of 44	1		ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000393380.6 link	c.1146T>C	p.Asn382Asn	synonymous_variant	Exon 7 of 12	1		ENSP00000377042.2	Q5T1H1-4
EYS	ENST00000342421.9 link	c.1146T>C	p.Asn382Asn	synonymous_variant	Exon 5 of 9	1		ENSP00000341818.5	Q5T1H1-2

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

79538

AN:

151706

Hom.:

20891

Cov.:

show subpopulations

Gnomad AFR

AF:

0.536

Gnomad AMI

AF:

0.654

Gnomad AMR

AF:

0.538

Gnomad ASJ

AF:

0.575

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.526

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.528

GnomAD2 exomes

AF:

0.519

AC:

129770

AN:

249798

AF XY:

0.519

show subpopulations

Gnomad AFR exome

AF:

0.528

Gnomad AMR exome

AF:

0.558

Gnomad ASJ exome

AF:

0.578

Gnomad EAS exome

AF:

0.443

Gnomad FIN exome

AF:

0.536

Gnomad NFE exome

AF:

0.508

Gnomad OTH exome

AF:

0.524

GnomAD4 exome

AF:

0.510

AC:

702437

AN:

1377606

Hom.:

180371

Cov.:

AF XY:

0.511

AC XY:

352198

AN XY:

689744

show subpopulations

African (AFR)

AF:

0.532

AC:

16788

AN:

31578

American (AMR)

AF:

0.554

AC:

24624

AN:

44412

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

14526

AN:

25488

East Asian (EAS)

AF:

0.444

AC:

17362

AN:

39092

South Asian (SAS)

AF:

0.526

AC:

44250

AN:

84146

European-Finnish (FIN)

AF:

0.536

AC:

28515

AN:

53222

Middle Eastern (MID)

AF:

0.531

AC:

2968

AN:

5586

European-Non Finnish (NFE)

AF:

0.506

AC:

524025

AN:

1036618

Other (OTH)

AF:

0.511

AC:

29379

AN:

57464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

14458

28917

43375

57834

72292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14854

29708

44562

59416

74270

<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:

0.524

AC:

79619

AN:

151824

Hom.:

20917

Cov.:

AF XY:

0.529

AC XY:

39214

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.536

AC:

22215

AN:

41410

American (AMR)

AF:

0.538

AC:

8176

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.575

AC:

1995

AN:

3468

East Asian (EAS)

AF:

0.468

AC:

2411

AN:

5156

South Asian (SAS)

AF:

0.537

AC:

2582

AN:

4810

European-Finnish (FIN)

AF:

0.539

AC:

5698

AN:

10562

Middle Eastern (MID)

AF:

0.514

AC:

149

AN:

290

European-Non Finnish (NFE)

AF:

0.511

AC:

34689

AN:

67922

Other (OTH)

AF:

0.526

AC:

1110

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1924

3849

5773

7698

9622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<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:

0.516

Hom.:

34166

Bravo

AF:

0.524

Asia WGS

AF:

0.475

AC:

1648

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:10

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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. -

Apr 17, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 25

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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 13, 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

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.10

(source)

DANN

Benign

0.27

PhyloP100

0.0020

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over