rs1041522

Variant names:

• chr6-65119497-C-T
• rs1041522
• NM_001142800.2:c.2024-61770G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142800.2(EYS):​c.2024-61770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,744 control chromosomes in the GnomAD database, including 23,018 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23018 hom., cov: 30)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.2024-61770G>A		intron_variant	Intron 12 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.2024-61770G>A		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.2024-61770G>A		intron_variant	Intron 12 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.2024-61770G>A		intron_variant	Intron 12 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82039 AN: 151626 Hom.: 22982 Cov.: 30

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.523

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.541 AC: 82131 AN: 151744 Hom.: 23018 Cov.: 30 AF XY: 0.539 AC XY: 39913 AN XY: 74116

African (AFR) AF: 0.658 AC: 27221 AN: 41380

American (AMR) AF: 0.449 AC: 6843 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1740 AN: 3466

East Asian (EAS) AF: 0.175 AC: 900 AN: 5148

South Asian (SAS) AF: 0.456 AC: 2193 AN: 4804

European-Finnish (FIN) AF: 0.581 AC: 6097 AN: 10494

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.522 AC: 35465 AN: 67898

Other (OTH) AF: 0.522 AC: 1097 AN: 2102

Alfa AF: 0.524 Hom.: 88520

Bravo AF: 0.532

Asia WGS AF: 0.345 AC: 1204 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.15
PhyloP100		-0.58
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: rs1041522; hg19: chr6-65829390;