NM_001142800.2:c.5705A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

23 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 -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 Benign/Likely_benign. ClinVar VariationId is 137256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

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.5705A>T	p.Asn1902Ile	missense	Exon 27 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.5705A>T	p.Asn1902Ile	missense	Exon 27 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.5705A>T	p.Asn1902Ile	missense	Exon 27 of 43	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.5705A>T	p.Asn1902Ile	missense	Exon 27 of 44	ENSP00000359655.3	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

GnomAD2 exomes

AF:

0.305

AC:

39820

AN:

130680

AF XY:

0.305

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 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

African (AFR)

AF:

0.202

AC:

6005

AN:

29778

American (AMR)

AF:

0.286

AC:

8860

AN:

30938

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

7056

AN:

24662

East Asian (EAS)

AF:

0.460

AC:

15557

AN:

33798

South Asian (SAS)

AF:

0.290

AC:

21134

AN:

72830

European-Finnish (FIN)

AF:

0.347

AC:

17036

AN:

49026

Middle Eastern (MID)

AF:

0.291

AC:

1637

AN:

5626

European-Non Finnish (NFE)

AF:

0.292

AC:

311585

AN:

1066330

Other (OTH)

AF:

0.302

AC:

17162

AN:

56904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

12329

24658

36987

49316

61645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10514

21028

31542

42056

52570

<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:

0.277

AC:

41992

AN:

151574

Hom.:

5939

Cov.:

AF XY:

0.281

AC XY:

20780

AN XY:

74058

show subpopulations

African (AFR)

AF:

0.207

AC:

8586

AN:

41462

American (AMR)

AF:

0.284

AC:

4312

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

951

AN:

3462

East Asian (EAS)

AF:

0.465

AC:

2401

AN:

5164

South Asian (SAS)

AF:

0.288

AC:

1388

AN:

4818

European-Finnish (FIN)

AF:

0.348

AC:

3666

AN:

10538

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19518

AN:

67628

Other (OTH)

AF:

0.294

AC:

617

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1521

3042

4563

6084

7605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.280

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Retinitis pigmentosa (2)

Retinitis pigmentosa 25 (2)

not provided (1)

Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0011

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

0.30

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.9

REVEL

Benign

0.14

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

0.85

Vest4

0.27

MPC

0.018

ClinPred

0.019

GERP RS

-1.4

Varity_R

0.17

gMVP

0.034

Mutation Taster

=91/9

polymorphism (auto)

(source)

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

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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