rs2050621

Positions:

• chr6-64535334-A-G
• chr6-64535334-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.5644+54889T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,016 control chromosomes in the GnomAD database, including 10,306 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 0.34 (10306 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.5644+54889T>C		intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.5644+54889T>C		intron_variant			NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.5644+54889T>C		intron_variant		5	NM_001142800.2	ENSP00000424243	A2
EYS	ENST00000370621.7	c.5644+54889T>C		intron_variant		1		ENSP00000359655	P2

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50915 AN: 151898 Hom.: 10269 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.336 AC: 51006 AN: 152016 Hom.: 10306 Cov.: 32 AF XY: 0.336 AC XY: 24943 AN XY: 74304

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.295

Alfa AF: 0.266 Hom.: 1518

Bravo AF: 0.350

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.0
DANN	Benign	0.65

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: rs2050621; hg19: chr6-65245227;