rs2146758

chr6-64880291-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.2992+6406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,630 control chromosomes in the GnomAD database, including 23,972 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 0.55 (23972 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.2992+6406G>A		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.2992+6406G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.2992+6406G>A		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.2992+6406G>A		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83835 AN: 151512 Hom.: 23960 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.553 AC: 83867 AN: 151630 Hom.: 23972 Cov.: 31 AF XY: 0.553 AC XY: 41002 AN XY: 74122

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.563

Alfa AF: 0.599 Hom.: 12071

Bravo AF: 0.539

Asia WGS AF: 0.401 AC: 1395 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.0
Dann	Benign	0.34

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: rs2146758; hg19: chr6-65590184;