rs644929

chr6-64458883-A-Gchr6-64458883-A-T

Variant summary

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

The NM_001142800.2(EYS):c.5645-19531T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,946 control chromosomes in the GnomAD database, including 13,816 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 0.41 (13816 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.5645-19531T>C		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.5645-19531T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.5645-19531T>C		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.5645-19531T>C		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62264 AN: 151828 Hom.: 13778 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.410 AC: 62353 AN: 151946 Hom.: 13816 Cov.: 32 AF XY: 0.410 AC XY: 30441 AN XY: 74270

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.390

Alfa AF: 0.195 Hom.: 474

Bravo AF: 0.422

Asia WGS AF: 0.403 AC: 1401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.24
Dann	Benign	0.69

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: rs644929; hg19: chr6-65168776;