dbSNP rs4710520: EYS:c.862+22007A>G (chr6-65468587-T-C) – 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.862+22007A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 152,092 control chromosomes in the GnomAD database, including 943 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 0.097 ( 943 hom., cov: 32)

Consequence

EYS
NM_001142800.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0810

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=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.862+22007A>G	intron_variant	Intron 5 of 42	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.862+22007A>G	intron_variant	Intron 5 of 43		NP_001278938.1	Q5T1H1-3
EYS	NM_001142801.2 link	c.862+22007A>G	intron_variant	Intron 5 of 11		NP_001136273.1	Q5T1H1-4
EYS	NM_198283.2 link	c.862+22007A>G	intron_variant	Intron 4 of 9		NP_938024.1	Q5T1H1-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EYS	ENST00000503581.6 link	c.862+22007A>G	intron_variant	Intron 5 of 42	5	NM_001142800.2	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7 link	c.862+22007A>G	intron_variant	Intron 5 of 43	1		ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000393380.6 link	c.862+22007A>G	intron_variant	Intron 5 of 11	1		ENSP00000377042.2	Q5T1H1-4
EYS	ENST00000342421.9 link	c.862+22007A>G	intron_variant	Intron 3 of 8	1		ENSP00000341818.5	Q5T1H1-2

Frequencies

GnomAD3 genomes

AF:

0.0970

AC:

14744

AN:

151976

Hom.:

942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0276

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.0502

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.121

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

GnomAD4 genome

AF:

0.0970

AC:

14750

AN:

152092

Hom.:

943

Cov.:

AF XY:

0.0987

AC XY:

7341

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0275

AC:

1143

AN:

41532

American (AMR)

AF:

0.126

AC:

1916

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

468

AN:

3466

East Asian (EAS)

AF:

0.0503

AC:

260

AN:

5168

South Asian (SAS)

AF:

0.184

AC:

888

AN:

4816

European-Finnish (FIN)

AF:

0.114

AC:

1205

AN:

10594

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8524

AN:

67960

Other (OTH)

AF:

0.122

AC:

258

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

668

1336

2004

2672

3340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.111

Hom.:

1534

Bravo

AF:

0.0928

Asia WGS

AF:

0.111

AC:

386

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.0

(source)

DANN

Benign

0.77

PhyloP100

-0.081

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over