rs16880108

Positions:

• chr6-64563602-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.5644+26621A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,022 control chromosomes in the GnomAD database, including 4,169 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 0.22 (4169 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.5644+26621A>G		intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.5644+26621A>G		intron_variant			NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.5644+26621A>G		intron_variant		5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.5644+26621A>G		intron_variant		1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33462 AN: 151904 Hom.: 4164 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.220 AC: 33478 AN: 152022 Hom.: 4169 Cov.: 32 AF XY: 0.224 AC XY: 16639 AN XY: 74300

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.243

Alfa AF: 0.239 Hom.: 1617

Bravo AF: 0.221

Asia WGS AF: 0.306 AC: 1061 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.80

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: rs16880108; hg19: chr6-65273495;