6-64307084-TGAGAGAGAGAGA-TGAGAGAGAGA

Variant names:

• chr6-64307084-TGA-T
• rs35395170
• NM_001142800.2:c.6079-4_6079-3delTC

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.6079-4_6079-3delTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 860,580 control chromosomes in the GnomAD database, including 81,349 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (34426 hom., cov: 0)
  • Exomes 𝑓: 0.52 (46923 hom.)
• Consequence: EYS NM_001142800.2 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.762
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 6-64307084-TGA-T is Benign according to our data. Variant chr6-64307084-TGA-T is described in ClinVar as Benign. ClinVar VariationId is 196616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.7 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.6079-4_6079-3delTC		splice_region intron	N/A	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.6079-4_6079-3delTC		splice_region 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.6079-4_6079-3delTC		splice_region intron	N/A	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.6079-4_6079-3delTC		splice_region intron	N/A	ENSP00000359655.3	Q5T1H1-3

Frequencies

GnomAD3 genomes AF: 0.680 AC: 101866 AN: 149726 Hom.: 34406 Cov.: 0

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.668

GnomAD2 exomes AF: 0.551 AC: 51515 AN: 93566 AF XY: 0.546

Gnomad AFR exome AF: 0.565

Gnomad AMR exome AF: 0.553

Gnomad ASJ exome AF: 0.542

Gnomad EAS exome AF: 0.503

Gnomad FIN exome AF: 0.573

Gnomad NFE exome AF: 0.557

Gnomad OTH exome AF: 0.548

GnomAD4 exome AF: 0.515 AC: 366350 AN: 710750 Hom.: 46923 AF XY: 0.517 AC XY: 191570 AN XY: 370368

African (AFR) AF: 0.515 AC: 8945 AN: 17376

American (AMR) AF: 0.506 AC: 13610 AN: 26882

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 10066 AN: 19080

East Asian (EAS) AF: 0.474 AC: 13416 AN: 28278

South Asian (SAS) AF: 0.519 AC: 29973 AN: 57746

European-Finnish (FIN) AF: 0.532 AC: 22719 AN: 42686

Middle Eastern (MID) AF: 0.580 AC: 2363 AN: 4074

European-Non Finnish (NFE) AF: 0.515 AC: 247515 AN: 480314

Other (OTH) AF: 0.517 AC: 17743 AN: 34314

GnomAD4 genome AF: 0.680 AC: 101929 AN: 149830 Hom.: 34426 Cov.: 0 AF XY: 0.676 AC XY: 49371 AN XY: 73020

African (AFR) AF: 0.673 AC: 27562 AN: 40958

American (AMR) AF: 0.672 AC: 10091 AN: 15010

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2497 AN: 3458

East Asian (EAS) AF: 0.488 AC: 2479 AN: 5084

South Asian (SAS) AF: 0.707 AC: 3343 AN: 4730

European-Finnish (FIN) AF: 0.643 AC: 6526 AN: 10150

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.706 AC: 47414 AN: 67176

Other (OTH) AF: 0.670 AC: 1382 AN: 2062

Alfa AF: 0.573 Hom.: 2265

Bravo AF: 0.677

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.76
Mutation Taster		=99/1	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: rs35395170; hg19: chr6-65016977; COSMIC: COSV65484750;