rs2993117

chr6-64533352-A-G

Variant summary

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

The NM_001142800.2(EYS):c.5644+56871T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,120 control chromosomes in the GnomAD database, including 4,475 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 0.16 (4475 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.5644+56871T>C		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.5644+56871T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.5644+56871T>C		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.5644+56871T>C		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24306 AN: 152002 Hom.: 4457 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0835

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.0402

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0378

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.160 AC: 24373 AN: 152120 Hom.: 4475 Cov.: 32 AF XY: 0.159 AC XY: 11795 AN XY: 74396

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.0837

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.0740

Gnomad4 FIN AF: 0.0402

Gnomad4 NFE AF: 0.0378

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0577 Hom.: 796

Bravo AF: 0.176

Asia WGS AF: 0.111 AC: 385 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.5
Dann	Benign	0.67

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: rs2993117; hg19: chr6-65243245;