6-64307084-TGAGAGAGAGAGA-TGAGAGAGA

Variant names:

• chr6-64307084-TGAGA-T
• rs35395170
• NM_001142800.2:c.6079-6_6079-3delTCTC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001142800.2(EYS):​c.6079-6_6079-3delTCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 754,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., cov: 0)
  • Exomes 𝑓: 0.073 (0 hom.)
• Consequence: EYS NM_001142800.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 6-64307084-TGAGA-T is Benign according to our data. Variant chr6-64307084-TGAGA-T is described in ClinVar as Benign. ClinVar VariationId is 1165561.Status of the report is criteria_provided_single_submitter, 1 stars.

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.6079-6_6079-3delTCTC		splice_region intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.6079-6_6079-3delTCTC		splice_region 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.6079-6_6079-3delTCTC		splice_region intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.6079-6_6079-3delTCTC		splice_region intron	N/A	ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.000542 AC: 81 AN: 149376 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00147

Gnomad ASJ AF: 0.000581

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00130

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000463

Gnomad OTH AF: 0.000977

GnomAD2 exomes AF: 0.103 AC: 9665 AN: 93566 AF XY: 0.106

Gnomad AFR exome AF: 0.0944

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.0600

Gnomad FIN exome AF: 0.0643

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0734 AC: 44442 AN: 605402 Hom.: 0 AF XY: 0.0753 AC XY: 23575 AN XY: 313104

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0728 AC: 1093 AN: 15010

American (AMR) AF: 0.0885 AC: 2090 AN: 23614

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 1347 AN: 15172

East Asian (EAS) AF: 0.0337 AC: 936 AN: 27750

South Asian (SAS) AF: 0.103 AC: 4797 AN: 46494

European-Finnish (FIN) AF: 0.0545 AC: 1987 AN: 36426

Middle Eastern (MID) AF: 0.0470 AC: 168 AN: 3576

European-Non Finnish (NFE) AF: 0.0733 AC: 29961 AN: 408490

Other (OTH) AF: 0.0715 AC: 2063 AN: 28870

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000549 AC: 82 AN: 149474 Hom.: 0 Cov.: 0 AF XY: 0.000687 AC XY: 50 AN XY: 72808

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000293 AC: 12 AN: 40942

American (AMR) AF: 0.00147 AC: 22 AN: 14986

Ashkenazi Jewish (ASJ) AF: 0.000581 AC: 2 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5088

South Asian (SAS) AF: 0.00 AC: 0 AN: 4730

European-Finnish (FIN) AF: 0.00130 AC: 13 AN: 10038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000463 AC: 31 AN: 66978

Other (OTH) AF: 0.000967 AC: 2 AN: 2068

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0961 Hom.: 2265

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Retinitis pigmentosa 25 Benign:1

Sep 27, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.76
Mutation Taster		=90/10	polymorphism

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;