rs7743515

Variant names:

• chr6-64886866-G-A
• rs7743515
• NM_001142800.2:c.2847-24C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-64886866-G-A
• chr6-64886866-G-C
• chr6-64886866-G-T

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.2847-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,424,302 control chromosomes in the GnomAD database, including 470,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52440 hom., cov: 31)
  • Exomes 𝑓: 0.81 (418371 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.904
• Publications: 12 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=-0.9).
• BP6: Variant 6-64886866-G-A is Benign according to our data. Variant chr6-64886866-G-A is described in ClinVar as Benign. ClinVar VariationId is 1175362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.2847-24C>T		intron_variant	Intron 18 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.2847-24C>T		intron_variant	Intron 18 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.2847-24C>T		intron_variant	Intron 18 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.2847-24C>T		intron_variant	Intron 18 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126094 AN: 151762 Hom.: 52399 Cov.: 31

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.835

GnomAD2 exomes AF: 0.828 AC: 97661 AN: 117980 AF XY: 0.824

Gnomad AFR exome AF: 0.849

Gnomad AMR exome AF: 0.867

Gnomad ASJ exome AF: 0.783

Gnomad EAS exome AF: 0.848

Gnomad FIN exome AF: 0.859

Gnomad NFE exome AF: 0.808

Gnomad OTH exome AF: 0.812

GnomAD4 exome AF: 0.810 AC: 1031007 AN: 1272422 Hom.: 418371 Cov.: 20 AF XY: 0.811 AC XY: 510918 AN XY: 630090

African (AFR) AF: 0.839 AC: 22344 AN: 26630

American (AMR) AF: 0.863 AC: 21894 AN: 25372

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 18503 AN: 23662

East Asian (EAS) AF: 0.849 AC: 27709 AN: 32648

South Asian (SAS) AF: 0.829 AC: 54751 AN: 66016

European-Finnish (FIN) AF: 0.855 AC: 41678 AN: 48766

Middle Eastern (MID) AF: 0.799 AC: 4335 AN: 5424

European-Non Finnish (NFE) AF: 0.804 AC: 796553 AN: 990474

Other (OTH) AF: 0.809 AC: 43240 AN: 53430

GnomAD4 genome AF: 0.831 AC: 126193 AN: 151880 Hom.: 52440 Cov.: 31 AF XY: 0.833 AC XY: 61831 AN XY: 74204

African (AFR) AF: 0.844 AC: 35002 AN: 41452

American (AMR) AF: 0.849 AC: 12895 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2761 AN: 3466

East Asian (EAS) AF: 0.851 AC: 4385 AN: 5152

South Asian (SAS) AF: 0.831 AC: 4009 AN: 4822

European-Finnish (FIN) AF: 0.862 AC: 9108 AN: 10562

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55289 AN: 67926

Other (OTH) AF: 0.835 AC: 1761 AN: 2110

Alfa AF: 0.811 Hom.: 68823

Bravo AF: 0.828

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 25 Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.25
DANN	Benign	0.19
PhyloP100		-0.90
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: rs7743515; hg19: chr6-65596759;