rs321494

Positions:

• chr6-63869914-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142800.2(EYS):​c.7056-5556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,828 control chromosomes in the GnomAD database, including 19,815 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 0.49 (19815 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.7056-5556G>A		intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.7056-5556G>A		intron_variant			NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.7056-5556G>A		intron_variant		5	NM_001142800.2	ENSP00000424243	A2
EYS	ENST00000370621.7	c.7056-5556G>A		intron_variant		1		ENSP00000359655	P2
EYS	ENST00000398580.3	c.370-5556G>A		intron_variant		5		ENSP00000381585

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73772 AN: 151710 Hom.: 19815 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.486 AC: 73775 AN: 151828 Hom.: 19815 Cov.: 31 AF XY: 0.487 AC XY: 36112 AN XY: 74210

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.531

Alfa AF: 0.524 Hom.: 3285

Bravo AF: 0.461

Asia WGS AF: 0.524 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.19

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: rs321494; hg19: chr6-64579807;