rs10104997

Positions:

• chr8-54527508-C-T

Variant summary

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

The ENST00000646684.1(RP1):​n.128-5188C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,094 control chromosomes in the GnomAD database, including 2,674 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 0.19 (2674 hom., cov: 31)
• Consequence: RP1 ENST00000646684.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

Genes affected

RP1 (HGNC:10263): (RP1 axonemal microtubule associated) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two doublecortin domains, which bind microtubules and regulate microtubule polymerization. The encoded protein is a photoreceptor microtubule-associated protein and is required for correct stacking of outer segment disc. This protein and the RP1L1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Because of its response to in vivo retinal oxygen levels, this protein was initially named ORP1 (oxygen-regulated protein-1). This protein was subsequently designated RP1 (retinitis pigmentosa 1) when it was found that mutations in this gene cause autosomal dominant retinitis pigmentosa. Mutations in this gene also cause autosomal recessive retinitis pigmentosa. Transcript variants resulted from an alternative promoter and alternative splicings have been found, which overlap the current reference sequence and has several exons upstream and downstream of the current reference sequence. However, the biological validity and full-length nature of some variants cannot be determined at this time.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RP1	ENST00000646684.1	n.128-5188C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28421 AN: 151974 Hom.: 2674 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.187 AC: 28454 AN: 152094 Hom.: 2674 Cov.: 31 AF XY: 0.189 AC XY: 14019 AN XY: 74342

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.180

Alfa AF: 0.187 Hom.: 2433

Bravo AF: 0.177

Asia WGS AF: 0.270 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.48
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10104997; hg19: chr8-55440068;