rs1490127

chr6-65707187-T-C

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 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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/exons	MANE	UniProt
EYS	NM_001142800.2	c.-500A>G		5_prime_UTR_variant	1/43	ENST00000503581.6
EYS	NM_001142801.2	c.-500A>G		5_prime_UTR_variant	1/12
EYS	NM_001292009.2	c.-500A>G		5_prime_UTR_variant	1/44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.-500A>G		5_prime_UTR_variant	1/43	5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.-500A>G		5_prime_UTR_variant	1/44	1		P2
EYS	ENST00000393380.6	c.-500A>G		5_prime_UTR_variant	1/12	1
EYS	ENST00000489873.1	n.28A>G		non_coding_transcript_exon_variant	1/5	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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Retinitis pigmentosa 25 Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Aug 29, 2019

- -

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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;