rs45628235

Variant names:

• chr6-65057741-G-A
• rs45628235
• NM_001142800.2:c.2024-14C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-65057741-G-A
• chr6-65057741-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142800.2(EYS):​c.2024-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,402,738 control chromosomes in the GnomAD database, including 37,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3422 hom., cov: 31)
  • Exomes 𝑓: 0.22 (33657 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.26
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-65057741-G-A is Benign according to our data. Variant chr6-65057741-G-A is described in ClinVar as Benign. ClinVar VariationId is 137269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.2024-14C>T		intron_variant	Intron 12 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.2024-14C>T		intron_variant	Intron 12 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.2024-14C>T		intron_variant	Intron 12 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.2024-14C>T		intron_variant	Intron 12 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30444 AN: 150418 Hom.: 3420 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.0507

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.215

GnomAD2 exomes AF: 0.243 AC: 32726 AN: 134792 AF XY: 0.251

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.0598

Gnomad FIN exome AF: 0.316

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.223 AC: 278888 AN: 1252202 Hom.: 33657 Cov.: 20 AF XY: 0.227 AC XY: 141772 AN XY: 624354

African (AFR) AF: 0.118 AC: 3315 AN: 28166

American (AMR) AF: 0.134 AC: 4257 AN: 31656

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 5986 AN: 23914

East Asian (EAS) AF: 0.0419 AC: 1465 AN: 34988

South Asian (SAS) AF: 0.268 AC: 19779 AN: 73752

European-Finnish (FIN) AF: 0.308 AC: 15081 AN: 49034

Middle Eastern (MID) AF: 0.217 AC: 1162 AN: 5346

European-Non Finnish (NFE) AF: 0.228 AC: 216780 AN: 952310

Other (OTH) AF: 0.209 AC: 11063 AN: 53036

GnomAD4 genome AF: 0.202 AC: 30450 AN: 150536 Hom.: 3422 Cov.: 31 AF XY: 0.206 AC XY: 15123 AN XY: 73446

African (AFR) AF: 0.125 AC: 5134 AN: 41048

American (AMR) AF: 0.152 AC: 2295 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 850 AN: 3458

East Asian (EAS) AF: 0.0510 AC: 261 AN: 5120

South Asian (SAS) AF: 0.258 AC: 1232 AN: 4780

European-Finnish (FIN) AF: 0.316 AC: 3227 AN: 10218

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.247 AC: 16696 AN: 67520

Other (OTH) AF: 0.217 AC: 453 AN: 2088

Alfa AF: 0.234 Hom.: 802

Bravo AF: 0.181

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 01, 2011

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The variant is found in ARRP panel(s). -

not specified Benign:1

Apr 17, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.35
PhyloP100		-3.3
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: rs45628235; hg19: chr6-65767634;