rs11752403

Positions:

• chr6-64351987-T-C

Variant summary

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

The NM_001142800.2(EYS):​c.6078+36703A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 151,658 control chromosomes in the GnomAD database, including 235 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 0.044 (235 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6078+36703A>G		intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.6078+36703A>G		intron_variant			NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6078+36703A>G		intron_variant		5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.6078+36703A>G		intron_variant		1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.0439 AC: 6653 AN: 151540 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0243

Gnomad EAS AF: 0.000585

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0439 AC: 6654 AN: 151658 Hom.: 235 Cov.: 32 AF XY: 0.0423 AC XY: 3133 AN XY: 74106

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.0243

Gnomad4 EAS AF: 0.000587

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.0445

Gnomad4 NFE AF: 0.0697

Gnomad4 OTH AF: 0.0450

Alfa AF: 0.0593 Hom.: 48

Bravo AF: 0.0419

Asia WGS AF: 0.0150 AC: 53 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
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: rs11752403; hg19: chr6-65061880;