dbSNP rs7775434: EYS:c.-332-35300T>A (chr6-65531293-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142800.2(EYS):c.-332-35300T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,986 control chromosomes in the GnomAD database, including 14,158 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 14158 hom., cov: 32)

Consequence

EYS
NM_001142800.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.462

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.-332-35300T>A	intron_variant	Intron 2 of 42	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.-332-35300T>A	intron_variant	Intron 2 of 43		NP_001278938.1	Q5T1H1-3
EYS	NM_001142801.2 link	c.-332-35300T>A	intron_variant	Intron 2 of 11		NP_001136273.1	Q5T1H1-4
EYS	NM_198283.2 link	c.-332-35300T>A	intron_variant	Intron 1 of 9		NP_938024.1	Q5T1H1-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EYS	ENST00000503581.6 link	c.-332-35300T>A	intron_variant	Intron 2 of 42	5	NM_001142800.2	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7 link	c.-332-35300T>A	intron_variant	Intron 2 of 43	1		ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000393380.6 link	c.-332-35300T>A	intron_variant	Intron 2 of 11	1		ENSP00000377042.2	Q5T1H1-4
EYS	ENST00000489873.1 link	n.196-35300T>A	intron_variant	Intron 2 of 4	1

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63465

AN:

151868

Hom.:

14140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.584

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.356

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.418

AC:

63538

AN:

151986

Hom.:

14158

Cov.:

AF XY:

0.416

AC XY:

30887

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.584

AC:

24213

AN:

41456

American (AMR)

AF:

0.408

AC:

6231

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

877

AN:

3466

East Asian (EAS)

AF:

0.476

AC:

2455

AN:

5154

South Asian (SAS)

AF:

0.345

AC:

1663

AN:

4814

European-Finnish (FIN)

AF:

0.332

AC:

3507

AN:

10570

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.345

AC:

23409

AN:

67944

Other (OTH)

AF:

0.356

AC:

750

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1825

3649

5474

7298

9123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.389

Hom.:

1512

Bravo

AF:

0.434

Asia WGS

AF:

0.430

AC:

1497

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.80

(source)

DANN

Benign

0.52

PhyloP100

-0.46

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over