rs7743515

chr6-64886866-G-Achr6-64886866-G-Cchr6-64886866-G-T

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.2847-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,424,302 control chromosomes in the GnomAD database, including 470,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52440 hom., cov: 31)
  • Exomes 𝑓: 0.81 (418371 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.904

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=-0.9).
• BP6: Variant 6-64886866-G-A is Benign according to our data. Variant chr6-64886866-G-A is described in ClinVar as [Benign]. Clinvar id is 1175362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.2847-24C>T		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.2847-24C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.2847-24C>T		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.2847-24C>T		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126094 AN: 151762 Hom.: 52399 Cov.: 31

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.835

GnomAD3 exomes AF: 0.828 AC: 97661 AN: 117980 Hom.: 40481 AF XY: 0.824 AC XY: 51931 AN XY: 63016

Gnomad AFR exome AF: 0.849

Gnomad AMR exome AF: 0.867

Gnomad ASJ exome AF: 0.783

Gnomad EAS exome AF: 0.848

Gnomad SAS exome AF: 0.827

Gnomad FIN exome AF: 0.859

Gnomad NFE exome AF: 0.808

Gnomad OTH exome AF: 0.812

GnomAD4 exome AF: 0.810 AC: 1031007 AN: 1272422 Hom.: 418371 Cov.: 20 AF XY: 0.811 AC XY: 510918 AN XY: 630090

Gnomad4 AFR exome AF: 0.839

Gnomad4 AMR exome AF: 0.863

Gnomad4 ASJ exome AF: 0.782

Gnomad4 EAS exome AF: 0.849

Gnomad4 SAS exome AF: 0.829

Gnomad4 FIN exome AF: 0.855

Gnomad4 NFE exome AF: 0.804

Gnomad4 OTH exome AF: 0.809

GnomAD4 genome AF: 0.831 AC: 126193 AN: 151880 Hom.: 52440 Cov.: 31 AF XY: 0.833 AC XY: 61831 AN XY: 74204

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.862

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.835

Alfa AF: 0.810 Hom.: 59004

Bravo AF: 0.828

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	-0.90
Cadd	Benign	0.25
Dann	Benign	0.19

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: rs7743515; hg19: chr6-65596759;