rs9342097

Variant names:

• chr6-64011163-T-G
• rs9342097
• NM_001142800.2:c.6726-11980A>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.6726-11980A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,012 control chromosomes in the GnomAD database, including 7,729 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 0.31 (7729 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381
• Publications: 3 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

LOC107986608 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6726-11980A>C		intron_variant	Intron 33 of 42	ENST00000503581.6	NP_001136272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6726-11980A>C		intron_variant	Intron 33 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.6726-11980A>C		intron_variant	Intron 33 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.39-11980A>C		intron_variant	Intron 1 of 9	5		ENSP00000381585.3

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47734 AN: 151894 Hom.: 7724 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.314 AC: 47752 AN: 152012 Hom.: 7729 Cov.: 32 AF XY: 0.311 AC XY: 23085 AN XY: 74300

African (AFR) AF: 0.256 AC: 10615 AN: 41460

American (AMR) AF: 0.269 AC: 4107 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1244 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1553 AN: 5170

South Asian (SAS) AF: 0.400 AC: 1931 AN: 4828

European-Finnish (FIN) AF: 0.289 AC: 3049 AN: 10540

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23875 AN: 67960

Other (OTH) AF: 0.346 AC: 731 AN: 2114

Alfa AF: 0.345 Hom.: 36452

Bravo AF: 0.310

Asia WGS AF: 0.326 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.8
DANN	Benign	0.76
PhyloP100		0.38
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: rs9342097; hg19: chr6-64721056;