6-65295847-GAA-GA

Variant names:

• chr6-65295847-GA-G
• rs35045551
• NM_001142800.2:c.2023+15delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001142800.2(EYS):​c.2023+15delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0721 in 1,397,374 control chromosomes in the GnomAD database, including 3,599 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (231 hom., cov: 0)
  • Exomes 𝑓: 0.075 (3368 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.679
• Publications: 4 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 -16 ACMG points.

• BP6: Variant 6-65295847-GA-G is Benign according to our data. Variant chr6-65295847-GA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 357736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0838 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.2023+15delT		intron	N/A	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.2023+15delT		intron	N/A	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.2023+15delT		intron	N/A	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.2023+15delT		intron	N/A	ENSP00000359655.3	Q5T1H1-3
	EYS	ENST00000370615.3	TSL:3	n.476delT		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7605 AN: 149638 Hom.: 229 Cov.: 0

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.0676

Gnomad EAS AF: 0.0324

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0684

Gnomad OTH AF: 0.0663

GnomAD2 exomes AF: 0.0866 AC: 7874 AN: 90928 AF XY: 0.0934

Gnomad AFR exome AF: 0.0365

Gnomad AMR exome AF: 0.0480

Gnomad ASJ exome AF: 0.0937

Gnomad EAS exome AF: 0.0588

Gnomad FIN exome AF: 0.0542

Gnomad NFE exome AF: 0.0976

Gnomad OTH exome AF: 0.0972

GnomAD4 exome AF: 0.0747 AC: 93176 AN: 1247650 Hom.: 3368 Cov.: 35 AF XY: 0.0753 AC XY: 46340 AN XY: 615068

African (AFR) AF: 0.0272 AC: 747 AN: 27466

American (AMR) AF: 0.0411 AC: 970 AN: 23574

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 1651 AN: 22700

East Asian (EAS) AF: 0.0193 AC: 584 AN: 30294

South Asian (SAS) AF: 0.104 AC: 6716 AN: 64272

European-Finnish (FIN) AF: 0.0461 AC: 2070 AN: 44896

Middle Eastern (MID) AF: 0.131 AC: 689 AN: 5274

European-Non Finnish (NFE) AF: 0.0777 AC: 75946 AN: 977300

Other (OTH) AF: 0.0733 AC: 3803 AN: 51874

GnomAD4 genome AF: 0.0508 AC: 7604 AN: 149724 Hom.: 231 Cov.: 0 AF XY: 0.0496 AC XY: 3623 AN XY: 73038

African (AFR) AF: 0.0250 AC: 1016 AN: 40690

American (AMR) AF: 0.0362 AC: 543 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.0676 AC: 233 AN: 3448

East Asian (EAS) AF: 0.0329 AC: 169 AN: 5140

South Asian (SAS) AF: 0.0908 AC: 433 AN: 4768

European-Finnish (FIN) AF: 0.0377 AC: 379 AN: 10044

Middle Eastern (MID) AF: 0.0793 AC: 23 AN: 290

European-Non Finnish (NFE) AF: 0.0684 AC: 4605 AN: 67344

Other (OTH) AF: 0.0652 AC: 136 AN: 2086

Alfa AF: 0.0511 Hom.: 1193

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Retinitis Pigmentosa, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.68
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: rs35045551; hg19: chr6-66005740;