rs9345601

Variant names:

• chr6-65296077-G-A
• rs9345601
• NM_001142800.2:c.1809C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-65296077-G-A
• chr6-65296077-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001142800.2(EYS):​c.1809C>T​(p.Val603Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,548,970 control chromosomes in the GnomAD database, including 271,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V603V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.52 (22770 hom., cov: 33)
  • Exomes 𝑓: 0.59 (248609 hom.)
• Consequence: EYS NM_001142800.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 1.55
• Publications: 21 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-65296077-G-A is Benign according to our data. Variant chr6-65296077-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.1809C>T	p.Val603Val	synonymous	Exon 12 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.1809C>T	p.Val603Val	synonymous	Exon 12 of 44	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.1809C>T	p.Val603Val	synonymous	Exon 12 of 43	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.1809C>T	p.Val603Val	synonymous	Exon 12 of 44	ENSP00000359655.3	Q5T1H1-3
	EYS	ENST00000370615.3	TSL:3	n.247C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78928 AN: 151654 Hom.: 22755 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.581

GnomAD2 exomes AF: 0.625 AC: 97415 AN: 155874 AF XY: 0.625

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.763

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.917

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.584

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.591 AC: 825266 AN: 1397196 Hom.: 248609 Cov.: 41 AF XY: 0.593 AC XY: 408843 AN XY: 689088

African (AFR) AF: 0.265 AC: 8367 AN: 31522

American (AMR) AF: 0.745 AC: 26469 AN: 35532

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 13082 AN: 25112

East Asian (EAS) AF: 0.908 AC: 32399 AN: 35670

South Asian (SAS) AF: 0.660 AC: 52059 AN: 78878

European-Finnish (FIN) AF: 0.563 AC: 27723 AN: 49266

Middle Eastern (MID) AF: 0.542 AC: 3084 AN: 5692

European-Non Finnish (NFE) AF: 0.583 AC: 628020 AN: 1077598

Other (OTH) AF: 0.588 AC: 34063 AN: 57926

GnomAD4 genome AF: 0.520 AC: 78964 AN: 151774 Hom.: 22770 Cov.: 33 AF XY: 0.527 AC XY: 39100 AN XY: 74168

African (AFR) AF: 0.275 AC: 11369 AN: 41400

American (AMR) AF: 0.668 AC: 10163 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1818 AN: 3470

East Asian (EAS) AF: 0.906 AC: 4684 AN: 5170

South Asian (SAS) AF: 0.681 AC: 3288 AN: 4830

European-Finnish (FIN) AF: 0.570 AC: 6001 AN: 10524

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39578 AN: 67846

Other (OTH) AF: 0.586 AC: 1235 AN: 2108

Alfa AF: 0.567 Hom.: 13628

Bravo AF: 0.520

Asia WGS AF: 0.761 AC: 2640 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	4	Retinitis pigmentosa 25 (4)
-	-	2	not provided (2)
-	-	2	Retinitis pigmentosa (2)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.39
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs9345601; hg19: chr6-66005970; COSMIC: COSV108200820;