6-64557087-C-T

Position:

• chr6-64557087-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142800.2(EYS):​c.5644+33136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 151,616 control chromosomes in the GnomAD database, including 44,602 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44602 hom., cov: 30)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.5644+33136G>A		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.5644+33136G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.5644+33136G>A		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.5644+33136G>A		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115165 AN: 151498 Hom.: 44542 Cov.: 30

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.705

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.760 AC: 115281 AN: 151616 Hom.: 44602 Cov.: 30 AF XY: 0.759 AC XY: 56225 AN XY: 74034

Gnomad4 AFR AF: 0.918

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.776

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.708

Alfa AF: 0.729 Hom.: 5103

Bravo AF: 0.768

Asia WGS AF: 0.742 AC: 2566 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2782295; hg19: chr6-65266980;