rs1482451

Variant names:

• chr6-63887193-G-A
• rs1482451
• NM_001142800.2:c.7056-22835C>T

Variant summary

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

The NM_001142800.2(EYS):​c.7056-22835C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,784 control chromosomes in the GnomAD database, including 8,098 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 0.32 (8098 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.7056-22835C>T		intron_variant	Intron 35 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.7056-22835C>T		intron_variant	Intron 35 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.7056-22835C>T		intron_variant	Intron 35 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.7056-22835C>T		intron_variant	Intron 35 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.369-22835C>T		intron_variant	Intron 3 of 9	5		ENSP00000381585.3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48850 AN: 151666 Hom.: 8089 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.322 AC: 48881 AN: 151784 Hom.: 8098 Cov.: 32 AF XY: 0.321 AC XY: 23792 AN XY: 74174

African (AFR) AF: 0.345 AC: 14274 AN: 41354

American (AMR) AF: 0.381 AC: 5818 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1226 AN: 3462

East Asian (EAS) AF: 0.280 AC: 1443 AN: 5162

South Asian (SAS) AF: 0.347 AC: 1667 AN: 4798

European-Finnish (FIN) AF: 0.219 AC: 2302 AN: 10504

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21114 AN: 67936

Other (OTH) AF: 0.327 AC: 691 AN: 2112

Alfa AF: 0.320 Hom.: 4675

Bravo AF: 0.335

Asia WGS AF: 0.290 AC: 1009 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.49
PhyloP100		1.5
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: rs1482451; hg19: chr6-64597086;