NM_001142800.2:c.2260-6814T>C

Variant names:

• chr6-64952728-A-G
• rs7767572
• NM_001142800.2:c.2260-6814T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142800.2(EYS):​c.2260-6814T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,040 control chromosomes in the GnomAD database, including 3,230 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 0.20 (3230 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.2260-6814T>C		intron_variant	Intron 14 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.2260-6814T>C		intron_variant	Intron 14 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.2260-6814T>C		intron_variant	Intron 14 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.2260-6814T>C		intron_variant	Intron 14 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30273 AN: 151924 Hom.: 3231 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.199 AC: 30283 AN: 152040 Hom.: 3230 Cov.: 32 AF XY: 0.200 AC XY: 14831 AN XY: 74332

African (AFR) AF: 0.138 AC: 5752 AN: 41534

American (AMR) AF: 0.157 AC: 2398 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3470

East Asian (EAS) AF: 0.245 AC: 1267 AN: 5180

South Asian (SAS) AF: 0.170 AC: 819 AN: 4828

European-Finnish (FIN) AF: 0.303 AC: 3207 AN: 10582

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15828 AN: 67880

Other (OTH) AF: 0.191 AC: 403 AN: 2110

Alfa AF: 0.210 Hom.: 6389

Bravo AF: 0.188

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.50
PhyloP100		0.20
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: rs7767572; hg19: chr6-65662621; COSMIC: COSV65538142;