rs1337512

chr6-64483927-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
EYS	NM_001142800.2	c.5645-44575A>C		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.5645-44575A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.5645-44575A>C		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.5645-44575A>C		intron_variant		1		P2

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

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.329

Alfa AF: 0.326 Hom.: 4124

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

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: rs1337512; hg19: chr6-65193820;