rs11752403

Variant names:

• chr6-64351987-T-C
• rs11752403
• NM_001142800.2:c.6078+36703A>G

Variant summary

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

The NM_001142800.2(EYS):​c.6078+36703A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 151,658 control chromosomes in the GnomAD database, including 235 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 0.044 (235 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6078+36703A>G		intron_variant	Intron 29 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.6078+36703A>G		intron_variant	Intron 29 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6078+36703A>G		intron_variant	Intron 29 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.6078+36703A>G		intron_variant	Intron 29 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.0439 AC: 6653 AN: 151540 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0243

Gnomad EAS AF: 0.000585

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0439 AC: 6654 AN: 151658 Hom.: 235 Cov.: 32 AF XY: 0.0423 AC XY: 3133 AN XY: 74106

African (AFR) AF: 0.0117 AC: 486 AN: 41466

American (AMR) AF: 0.0285 AC: 433 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.0243 AC: 84 AN: 3460

East Asian (EAS) AF: 0.000587 AC: 3 AN: 5112

South Asian (SAS) AF: 0.0319 AC: 154 AN: 4828

European-Finnish (FIN) AF: 0.0445 AC: 472 AN: 10616

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0697 AC: 4718 AN: 67658

Other (OTH) AF: 0.0450 AC: 95 AN: 2110

Alfa AF: 0.0603 Hom.: 99

Bravo AF: 0.0419

Asia WGS AF: 0.0150 AC: 53 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.71
PhyloP100		-0.19
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: rs11752403; hg19: chr6-65061880;