NM_001142800.2:c.2260-20766C>G

Variant names:

• chr6-64966680-G-C
• rs9354193
• NM_001142800.2:c.2260-20766C>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.2260-20766C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,052 control chromosomes in the GnomAD database, including 11,629 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 0.36 (11629 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• 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 (AMR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.2260-20766C>G		intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.2260-20766C>G		intron	N/A	NP_001278938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.2260-20766C>G		intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.2260-20766C>G		intron	N/A	ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53975 AN: 151934 Hom.: 11617 Cov.: 32

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.355 AC: 54008 AN: 152052 Hom.: 11629 Cov.: 32 AF XY: 0.353 AC XY: 26249 AN XY: 74310

African (AFR) AF: 0.0993 AC: 4121 AN: 41500

American (AMR) AF: 0.494 AC: 7550 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1761 AN: 3464

East Asian (EAS) AF: 0.428 AC: 2204 AN: 5154

South Asian (SAS) AF: 0.386 AC: 1861 AN: 4820

European-Finnish (FIN) AF: 0.364 AC: 3842 AN: 10552

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31221 AN: 67980

Other (OTH) AF: 0.413 AC: 872 AN: 2110

Alfa AF: 0.279 Hom.: 789

Bravo AF: 0.353

Asia WGS AF: 0.392 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.87
DANN	Benign	0.51
PhyloP100		-0.12
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: rs9354193; hg19: chr6-65676573;