6-64557087-C-T

Variant names:

• chr6-64557087-C-T
• rs2782295
• NM_001142800.2:c.5644+33136G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

EYS Gene-Disease associations (from GenCC):

• EYS-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• retinitis pigmentosa 25

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.5644+33136G>A		intron	N/A	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.5644+33136G>A		intron	N/A	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.5644+33136G>A		intron	N/A	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.5644+33136G>A		intron	N/A	ENSP00000359655.3	Q5T1H1-3

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

African (AFR) AF: 0.918 AC: 38059 AN: 41468

American (AMR) AF: 0.744 AC: 11297 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2257 AN: 3466

East Asian (EAS) AF: 0.664 AC: 3407 AN: 5134

South Asian (SAS) AF: 0.776 AC: 3732 AN: 4810

European-Finnish (FIN) AF: 0.703 AC: 7395 AN: 10514

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 46865 AN: 67720

Other (OTH) AF: 0.708 AC: 1490 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.29
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2782295; hg19: chr6-65266980;