Genetic Variant EYS:c.6079-6_6079-3delTCTC (chr6-64307084-TGAGA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001142800.2(EYS):c.6079-6_6079-3delTCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 754,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 0)

Exomes 𝑓: 0.073 ( 0 hom. )

Consequence

EYS
NM_001142800.2 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.762

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 -10 ACMG points.

BP6

Variant 6-64307084-TGAGA-T is Benign according to our data. Variant chr6-64307084-TGAGA-T is described in ClinVar as [Benign]. Clinvar id is 1165561.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-64307084-TGAGA-T is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.6079-6_6079-3delTCTC		splice_region_variant, intron_variant	Intron 29 of 42	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.6079-6_6079-3delTCTC		splice_region_variant, intron_variant	Intron 29 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.6079-6_6079-3delTCTC		splice_region_variant, intron_variant	Intron 29 of 42	5	NM_001142800.2	ENSP00000424243.1		Q5T1H1-1
EYS	ENST00000370621.7 link	c.6079-6_6079-3delTCTC		splice_region_variant, intron_variant	Intron 29 of 43	1		ENSP00000359655.3		Q5T1H1-3

Frequencies

GnomAD3 genomes

AF:

0.000542

AC:

AN:

149376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000269

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00147

Gnomad ASJ

AF:

0.000581

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00130

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000463

Gnomad OTH

AF:

0.000977

GnomAD4 exome

AF:

0.0734

AC:

44442

AN:

605402

Hom.:

AF XY:

0.0753

AC XY:

23575

AN XY:

313104

show subpopulations

Gnomad4 AFR exome

AF:

0.0728

Gnomad4 AMR exome

AF:

0.0885

Gnomad4 ASJ exome

AF:

0.0888

Gnomad4 EAS exome

AF:

0.0337

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.0545

Gnomad4 NFE exome

AF:

0.0733

Gnomad4 OTH exome

AF:

0.0715

GnomAD4 genome

AF:

0.000549

AC:

AN:

149474

Hom.:

Cov.:

AF XY:

0.000687

AC XY:

AN XY:

72808

show subpopulations

Gnomad4 AFR

AF:

0.000293

Gnomad4 AMR

AF:

0.00147

Gnomad4 ASJ

AF:

0.000581

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00130

Gnomad4 NFE

AF:

0.000463

Gnomad4 OTH

AF:

0.000967

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 25

Benign:1

Sep 27, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

6-64307084-TGAGAGAGAGAGA-TGAGAGAGA

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