rs66502009

Positions:

• chr6-63999014-A-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.6834+61T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,027,904 control chromosomes in the GnomAD database, including 71,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7796 hom., cov: 31)
  • Exomes 𝑓: 0.38 (63692 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.422

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]

LOC107986608 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-63999014-A-C is Benign according to our data. Variant chr6-63999014-A-C is described in ClinVar as [Benign]. Clinvar id is 1175356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.6834+61T>G		intron_variant		ENST00000503581.6
LOC107986608	XR_007059629.1	n.317-22373A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.6834+61T>G		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.6834+61T>G		intron_variant		1		P2
EYS	ENST00000398580.3	c.148+61T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45781 AN: 151904 Hom.: 7797 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.375 AC: 328599 AN: 875882 Hom.: 63692 AF XY: 0.379 AC XY: 170786 AN XY: 450548

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.372

GnomAD4 genome AF: 0.301 AC: 45788 AN: 152022 Hom.: 7796 Cov.: 31 AF XY: 0.299 AC XY: 22221 AN XY: 74282

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.339

Alfa AF: 0.334 Hom.: 1153

Bravo AF: 0.292

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.80
CADD	Benign	0.82
DANN	Benign	0.84

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: rs66502009; hg19: chr6-64708907; COSMIC: COSV65474781;