rs16895338

Positions:

• chr6-64500697-C-T

Variant summary

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

The NM_001142800.2(EYS):​c.5645-61345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,882 control chromosomes in the GnomAD database, including 5,472 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 0.25 (5472 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.5645-61345G>A		intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.5645-61345G>A		intron_variant			NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.5645-61345G>A		intron_variant		5	NM_001142800.2	ENSP00000424243	A2
EYS	ENST00000370621.7	c.5645-61345G>A		intron_variant		1		ENSP00000359655	P2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38432 AN: 151766 Hom.: 5475 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.253 AC: 38429 AN: 151882 Hom.: 5472 Cov.: 32 AF XY: 0.255 AC XY: 18907 AN XY: 74214

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.280

Alfa AF: 0.288 Hom.: 3798

Bravo AF: 0.246

Asia WGS AF: 0.283 AC: 981 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.56

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: rs16895338; hg19: chr6-65210590;