rs1337512

Variant names:

• chr6-64483927-T-G
• rs1337512
• NM_001142800.2:c.5645-44575A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142800.2(EYS):​c.5645-44575A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,556 control chromosomes in the GnomAD database, including 7,679 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 0.32 (7679 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 6 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.5645-44575A>C		intron_variant	Intron 26 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.5645-44575A>C		intron_variant	Intron 26 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.5645-44575A>C		intron_variant	Intron 26 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.5645-44575A>C		intron_variant	Intron 26 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47915 AN: 151438 Hom.: 7679 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.316 AC: 47935 AN: 151556 Hom.: 7679 Cov.: 32 AF XY: 0.319 AC XY: 23655 AN XY: 74038

African (AFR) AF: 0.242 AC: 10006 AN: 41422

American (AMR) AF: 0.317 AC: 4815 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1174 AN: 3456

East Asian (EAS) AF: 0.499 AC: 2547 AN: 5106

South Asian (SAS) AF: 0.313 AC: 1509 AN: 4822

European-Finnish (FIN) AF: 0.387 AC: 4087 AN: 10568

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22587 AN: 67714

Other (OTH) AF: 0.329 AC: 689 AN: 2094

Alfa AF: 0.325 Hom.: 4574

Bravo AF: 0.313

Asia WGS AF: 0.370 AC: 1286 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.74
DANN	Benign	0.70
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1337512; hg19: chr6-65193820;