rs1490127

Variant names:

• chr6-65707187-T-C
• rs1490127
• NM_001142800.2:c.-500A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142800.2(EYS):​c.-500A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,022 control chromosomes in the GnomAD database, including 3,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3551 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: EYS NM_001142800.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.349

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-65707187-T-C is Benign according to our data. Variant chr6-65707187-T-C is described in ClinVar as [Benign]. Clinvar id is 357762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-65707187-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.-500A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 43	ENST00000503581.6	NP_001136272.1
EYS	NM_001142800.2	c.-500A>G		5_prime_UTR_variant	Exon 1 of 43	ENST00000503581.6	NP_001136272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.-500A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 43	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000503581.6	c.-500A>G		5_prime_UTR_variant	Exon 1 of 43	5	NM_001142800.2	ENSP00000424243.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30966 AN: 151904 Hom.: 3545 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0714

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.148

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.204 AC: 30997 AN: 152022 Hom.: 3551 Cov.: 32 AF XY: 0.201 AC XY: 14908 AN XY: 74318

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.0708

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.147

Alfa AF: 0.195 Hom.: 630

Bravo AF: 0.211

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

EYS-related disorder Benign:1

Aug 30, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Retinitis pigmentosa 25 Benign:1

Aug 29, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Retinitis pigmentosa Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs1490127; hg19: chr6-66417080;