rs1482451

chr6-63887193-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EYS	NM_001142800.2	c.7056-22835C>T		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.7056-22835C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.7056-22835C>T		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.7056-22835C>T		intron_variant		1		P2
EYS	ENST00000398580.3	c.370-22835C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.327

Alfa AF: 0.321 Hom.: 4242

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1482451; hg19: chr6-64597086;