dbSNP rs12208631: EYS:c.6079-34554T>C (chr6-64341636-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001142800.2(EYS):c.6079-34554T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 151,790 control chromosomes in the GnomAD database, including 88 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 0.028 ( 88 hom., cov: 32)

Consequence

EYS
NM_001142800.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.240

Publications

1 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=-0.91).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0277 (4200/151790) while in subpopulation NFE AF = 0.0407 (2757/67748). AF 95% confidence interval is 0.0394. There are 88 homozygotes in GnomAd4. There are 1994 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 88 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.6079-34554T>C		intron_variant	Intron 29 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2 link	c.6079-34554T>C		intron_variant	Intron 29 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6 link	c.6079-34554T>C		intron_variant	Intron 29 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7 link	c.6079-34554T>C		intron_variant	Intron 29 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4199

AN:

151672

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00705

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0916

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.0226

Gnomad FIN

AF:

0.0260

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0407

Gnomad OTH

AF:

0.0400

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

GnomAD4 genome

AF:

0.0277

AC:

4200

AN:

151790

Hom.:

Cov.:

AF XY:

0.0269

AC XY:

1994

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.00703

AC:

292

AN:

41518

American (AMR)

AF:

0.0232

AC:

352

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.0916

AC:

317

AN:

3462

East Asian (EAS)

AF:

0.000195

AC:

AN:

5128

South Asian (SAS)

AF:

0.0228

AC:

110

AN:

4824

European-Finnish (FIN)

AF:

0.0260

AC:

276

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0407

AC:

2757

AN:

67748

Other (OTH)

AF:

0.0396

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

210

421

631

842

1052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0287

Hom.:

Bravo

AF:

0.0264

Asia WGS

AF:

0.0110

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.3

(source)

DANN

Benign

0.63

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism

(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