dbSNP rs10944813: EYS:c.-332-1332T>C (chr6-65497325-A-G) – 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.-332-1332T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,838 control chromosomes in the GnomAD database, including 7,047 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 0.30 ( 7047 hom., cov: 32)

Consequence

EYS
NM_001142800.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0920

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EYS	NM_001142800.2	MANE Select	c.-332-1332T>C	intron	N/A	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2		c.-332-1332T>C	intron	N/A	NP_001278938.1	Q5T1H1-3
EYS	NM_001142801.2		c.-332-1332T>C	intron	N/A	NP_001136273.1	Q5T1H1-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EYS	ENST00000503581.6	TSL:5 MANE Select	c.-332-1332T>C	intron	N/A	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7	TSL:1	c.-332-1332T>C	intron	N/A	ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000393380.6	TSL:1	c.-332-1332T>C	intron	N/A	ENSP00000377042.2	Q5T1H1-4

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45086

AN:

151720

Hom.:

7026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.332

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

GnomAD4 genome

AF:

0.297

AC:

45162

AN:

151838

Hom.:

7047

Cov.:

AF XY:

0.297

AC XY:

22026

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.387

AC:

16016

AN:

41414

American (AMR)

AF:

0.338

AC:

5152

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1202

AN:

3466

East Asian (EAS)

AF:

0.306

AC:

1576

AN:

5150

South Asian (SAS)

AF:

0.212

AC:

1024

AN:

4824

European-Finnish (FIN)

AF:

0.224

AC:

2373

AN:

10584

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16687

AN:

67850

Other (OTH)

AF:

0.328

AC:

690

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1576

3153

4729

6306

7882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<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:

0.272

Hom.:

8122

Bravo

AF:

0.312

Asia WGS

AF:

0.256

AC:

891

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.5

(source)

DANN

Benign

0.34

PhyloP100

0.092

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over