rs2146758

Variant names:

• chr6-64880291-C-T
• rs2146758
• NM_001142800.2:c.2992+6406G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

EYS Gene-Disease associations (from GenCC):

• EYS-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• retinitis pigmentosa 25

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.2992+6406G>A		intron_variant	Intron 19 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.2992+6406G>A		intron_variant	Intron 19 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.2992+6406G>A		intron_variant	Intron 19 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.2992+6406G>A		intron_variant	Intron 19 of 43	1		ENSP00000359655.3

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

African (AFR) AF: 0.445 AC: 18405 AN: 41360

American (AMR) AF: 0.602 AC: 9141 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2072 AN: 3466

East Asian (EAS) AF: 0.202 AC: 1041 AN: 5154

South Asian (SAS) AF: 0.531 AC: 2554 AN: 4808

European-Finnish (FIN) AF: 0.661 AC: 6972 AN: 10542

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.617 AC: 41808 AN: 67810

Other (OTH) AF: 0.563 AC: 1187 AN: 2110

Alfa AF: 0.598 Hom.: 13572

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
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2146758; hg19: chr6-65590184;