rs10626313

Positions:

• chr1-68429047-G-GCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000262340.6(RPE65):​c.*728_*729insAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (15091 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: RPE65 ENST00000262340.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

RPE65 (HGNC:10294): (retinoid isomerohydrolase RPE65) The protein encoded by this gene is a component of the vitamin A visual cycle of the retina which supplies the 11-cis retinal chromophore of the photoreceptors opsin visual pigments. It is a member of the carotenoid cleavage oxygenase superfamily. All members of this superfamily are non-heme iron oxygenases with a seven-bladed propeller fold and oxidatively cleave carotenoid carbon:carbon double bonds. However, the protein encoded by this gene has acquired a divergent function that involves the concerted O-alkyl ester cleavage of its all-trans retinyl ester substrate and all-trans to 11-cis double bond isomerization of the retinyl moiety. As such, it performs the essential enzymatic isomerization step in the synthesis of 11-cis retinal. Mutations in this gene are associated with early-onset severe blinding disorders such as Leber congenital. [provided by RefSeq, Oct 2017]

LOC124904198 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPE65	NM_000329.3	c.*728_*729insAG		3_prime_UTR_variant	14/14	ENST00000262340.6	NP_000320.1
LOC124904198	XR_007066164.1	n.71+8927_71+8928dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPE65	ENST00000262340.6	c.*728_*729insAG		3_prime_UTR_variant	14/14	1	NM_000329.3	ENSP00000262340	P1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64789 AN: 151536 Hom.: 15069 Cov.: 0

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.402

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.428 AC: 64852 AN: 151654 Hom.: 15091 Cov.: 0 AF XY: 0.435 AC XY: 32214 AN XY: 74106

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.404

Alfa AF: 0.376 Hom.: 1220

Asia WGS AF: 0.609 AC: 2084 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10626313; hg19: chr1-68894730;