dbSNP rs9445437: EYS:c.2382-26C>G (chr6-64912769-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142800.2(EYS):c.2382-26C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,299,052 control chromosomes in the GnomAD database, including 231,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35079 hom., cov: 32)

Exomes 𝑓: 0.58 ( 196766 hom. )

Consequence

EYS
NM_001142800.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.680

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-64912769-G-C is Benign according to our data. Variant chr6-64912769-G-C is described in ClinVar as [Benign]. Clinvar id is 1175365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.2382-26C>G		intron_variant	Intron 15 of 42	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.2382-26C>G		intron_variant	Intron 15 of 43		NP_001278938.1	Q5T1H1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6 link	c.2382-26C>G		intron_variant	Intron 15 of 42	5	NM_001142800.2	ENSP00000424243.1		Q5T1H1-1
EYS	ENST00000370621.7 link	c.2382-26C>G		intron_variant	Intron 15 of 43	1		ENSP00000359655.3		Q5T1H1-3

Frequencies

GnomAD3 genomes

AF:

0.665

AC:

101025

AN:

151824

Hom.:

35040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.876

Gnomad AMI

AF:

0.557

Gnomad AMR

AF:

0.642

Gnomad ASJ

AF:

0.699

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.578

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.655

GnomAD3 exomes

AF:

0.592

AC:

28353

AN:

47900

Hom.:

8712

AF XY:

0.587

AC XY:

13822

AN XY:

23534

show subpopulations

Gnomad AFR exome

AF:

0.891

Gnomad AMR exome

AF:

0.619

Gnomad ASJ exome

AF:

0.708

Gnomad EAS exome

AF:

0.391

Gnomad SAS exome

AF:

0.567

Gnomad FIN exome

AF:

0.581

Gnomad NFE exome

AF:

0.577

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.582

AC:

667395

AN:

1147108

Hom.:

196766

Cov.:

AF XY:

0.581

AC XY:

318660

AN XY:

548664

show subpopulations

Gnomad4 AFR exome

AF:

0.895

Gnomad4 AMR exome

AF:

0.632

Gnomad4 ASJ exome

AF:

0.693

Gnomad4 EAS exome

AF:

0.437

Gnomad4 SAS exome

AF:

0.560

Gnomad4 FIN exome

AF:

0.578

Gnomad4 NFE exome

AF:

0.575

Gnomad4 OTH exome

AF:

0.601

GnomAD4 genome

AF:

0.665

AC:

101118

AN:

151944

Hom.:

35079

Cov.:

AF XY:

0.662

AC XY:

49160

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.876

Gnomad4 AMR

AF:

0.642

Gnomad4 ASJ

AF:

0.699

Gnomad4 EAS

AF:

0.410

Gnomad4 SAS

AF:

0.554

Gnomad4 FIN

AF:

0.578

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.656

Alfa

AF:

0.503

Hom.:

1545

Bravo

AF:

0.677

Asia WGS

AF:

0.556

AC:

1934

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 25

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.52

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over