rs36133910

chr6-64388622-T-Cchr6-64388622-T-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.6078+68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,345,756 control chromosomes in the GnomAD database, including 60,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (5960 hom., cov: 32)
  • Exomes 𝑓: 0.30 (54149 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.562

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-64388622-T-C is Benign according to our data. Variant chr6-64388622-T-C is described in ClinVar as [Benign]. Clinvar id is 1175357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.6078+68A>G		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.6078+68A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.6078+68A>G		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.6078+68A>G		intron_variant		1		P2
	ENST00000424274.1	n.267+8910T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42119 AN: 151888 Hom.: 5956 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.298 AC: 356260 AN: 1193748 Hom.: 54149 AF XY: 0.298 AC XY: 175928 AN XY: 589550

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.277 AC: 42147 AN: 152008 Hom.: 5960 Cov.: 32 AF XY: 0.281 AC XY: 20862 AN XY: 74284

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.294

Alfa AF: 0.273 Hom.: 698

Bravo AF: 0.275

Asia WGS AF: 0.348 AC: 1205 AN: 3456

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	-0.86
Cadd	Benign	0.36
Dann	Benign	0.71

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: rs36133910; hg19: chr6-65098515; COSMIC: COSV65474589;