6-64591274-C-T

Variant names:

• chr6-64591274-C-T
• rs62415825
• NM_001142800.2:c.4593G>A

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.4593G>A​(p.Glu1531Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,551,080 control chromosomes in the GnomAD database, including 13,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (928 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12911 hom.)
• Consequence: EYS NM_001142800.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.395
• Publications: 8 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-64591274-C-T is Benign according to our data. Variant chr6-64591274-C-T is described in ClinVar as Benign. ClinVar VariationId is 93615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.395 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 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.4593G>A	p.Glu1531Glu	synonymous	Exon 26 of 43	NP_001136272.1
	EYS	NM_001292009.2		c.4593G>A	p.Glu1531Glu	synonymous	Exon 26 of 44	NP_001278938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.4593G>A	p.Glu1531Glu	synonymous	Exon 26 of 43	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.4593G>A	p.Glu1531Glu	synonymous	Exon 26 of 44	ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15354 AN: 151988 Hom.: 931 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0992

GnomAD2 exomes AF: 0.119 AC: 18242 AN: 153700 AF XY: 0.119

Gnomad AFR exome AF: 0.0306

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.0820

Gnomad EAS exome AF: 0.175

Gnomad FIN exome AF: 0.0820

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.132 AC: 185120 AN: 1398974 Hom.: 12911 Cov.: 35 AF XY: 0.132 AC XY: 91042 AN XY: 689994

African (AFR) AF: 0.0303 AC: 958 AN: 31584

American (AMR) AF: 0.135 AC: 4827 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.0797 AC: 2006 AN: 25166

East Asian (EAS) AF: 0.145 AC: 5169 AN: 35732

South Asian (SAS) AF: 0.105 AC: 8284 AN: 79222

European-Finnish (FIN) AF: 0.0808 AC: 3981 AN: 49268

Middle Eastern (MID) AF: 0.0574 AC: 327 AN: 5694

European-Non Finnish (NFE) AF: 0.141 AC: 152361 AN: 1078616

Other (OTH) AF: 0.124 AC: 7207 AN: 57988

GnomAD4 genome AF: 0.101 AC: 15349 AN: 152106 Hom.: 928 Cov.: 32 AF XY: 0.0993 AC XY: 7381 AN XY: 74356

African (AFR) AF: 0.0365 AC: 1516 AN: 41538

American (AMR) AF: 0.125 AC: 1899 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3472

East Asian (EAS) AF: 0.165 AC: 852 AN: 5152

South Asian (SAS) AF: 0.112 AC: 541 AN: 4820

European-Finnish (FIN) AF: 0.0742 AC: 786 AN: 10598

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.135 AC: 9181 AN: 67966

Other (OTH) AF: 0.0982 AC: 207 AN: 2108

Alfa AF: 0.126 Hom.: 2556

Bravo AF: 0.105

Asia WGS AF: 0.122 AC: 422 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.9
DANN	Benign	0.34
PhyloP100		0.40
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: rs62415825; hg19: chr6-65301167; COSMIC: COSV58197760; COSMIC: COSV58197760;