Variant rs587278 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001142800.2(EYS):c.5928-35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,367,990 control chromosomes in the GnomAD database, including 339,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.72 ( 39780 hom., cov: 32)

Exomes 𝑓: 0.70 ( 299620 hom. )

Consequence

EYS
NM_001142800.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.363

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:

ENSG00000232120 (HGNC:):

ENSG00000232120 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-64388875-A-G is Benign according to our data. Variant chr6-64388875-A-G is described in ClinVar as [Benign]. Clinvar id is 1175358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2 linkuse as main transcript	c.5928-35T>C		intron_variant		ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 linkuse as main transcript	c.5928-35T>C		intron_variant			NP_001278938.1	Q5T1H1-3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
EYS	ENST00000503581.6 linkuse as main transcript	c.5928-35T>C	intron_variant	5	NM_001142800.2	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7 linkuse as main transcript	c.5928-35T>C	intron_variant	1		ENSP00000359655.3	Q5T1H1-3
ENSG00000232120	ENST00000424274.1 linkuse as main transcript	n.267+9163A>G	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.722

AC:

109700

AN:

151860

Hom.:

39744

Cov.:

show subpopulations

Gnomad AFR

AF:

0.792

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.716

Gnomad ASJ

AF:

0.725

Gnomad EAS

AF:

0.535

Gnomad SAS

AF:

0.712

Gnomad FIN

AF:

0.650

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.704

GnomAD3 exomes

AF:

0.697

AC:

63755

AN:

91408

Hom.:

22133

AF XY:

0.696

AC XY:

34698

AN XY:

49824

show subpopulations

Gnomad AFR exome

AF:

0.788

Gnomad AMR exome

AF:

0.729

Gnomad ASJ exome

AF:

0.726

Gnomad EAS exome

AF:

0.514

Gnomad SAS exome

AF:

0.710

Gnomad FIN exome

AF:

0.658

Gnomad NFE exome

AF:

0.711

Gnomad OTH exome

AF:

0.679

GnomAD4 exome

AF:

0.702

AC:

853163

AN:

1216012

Hom.:

299620

Cov.:

AF XY:

0.702

AC XY:

418616

AN XY:

596434

show subpopulations

Gnomad4 AFR exome

AF:

0.794

Gnomad4 AMR exome

AF:

0.718

Gnomad4 ASJ exome

AF:

0.714

Gnomad4 EAS exome

AF:

0.541

Gnomad4 SAS exome

AF:

0.709

Gnomad4 FIN exome

AF:

0.653

Gnomad4 NFE exome

AF:

0.706

Gnomad4 OTH exome

AF:

0.697

GnomAD4 genome

AF:

0.722

AC:

109792

AN:

151978

Hom.:

39780

Cov.:

AF XY:

0.719

AC XY:

53388

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.792

Gnomad4 AMR

AF:

0.716

Gnomad4 ASJ

AF:

0.725

Gnomad4 EAS

AF:

0.535

Gnomad4 SAS

AF:

0.711

Gnomad4 FIN

AF:

0.650

Gnomad4 NFE

AF:

0.711

Gnomad4 OTH

AF:

0.707

Alfa

AF:

0.720

Hom.:

8159

Bravo

AF:

0.725

Asia WGS

AF:

0.650

AC:

2257

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Retinitis pigmentosa 25

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

7.4

DANN

Benign

0.34

BranchPoint Hunter

1.0

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

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