rs10089685

Variant names:

• chr8-54518793-G-A
• rs10089685
• ENST00000646684.1:n.127+9245G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000646684.1(RP1):​n.127+9245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,148 control chromosomes in the GnomAD database, including 44,474 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 0.76 (44474 hom., cov: 32)
• Consequence: RP1 ENST00000646684.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 2 publications found

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]

RP1 Gene-Disease associations (from GenCC):

• RP1-related dominant retinopathy

  Inheritance: AD, SD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen
• retinitis pigmentosa 1

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• RP1-related recessive retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RP1	ENST00000646684.1	n.127+9245G>A		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114870 AN: 152028 Hom.: 44444 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.756 AC: 114954 AN: 152148 Hom.: 44474 Cov.: 32 AF XY: 0.754 AC XY: 56054 AN XY: 74368

African (AFR) AF: 0.576 AC: 23904 AN: 41480

American (AMR) AF: 0.724 AC: 11066 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3142 AN: 3468

East Asian (EAS) AF: 0.719 AC: 3727 AN: 5180

South Asian (SAS) AF: 0.752 AC: 3628 AN: 4822

European-Finnish (FIN) AF: 0.831 AC: 8801 AN: 10588

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 58014 AN: 68012

Other (OTH) AF: 0.777 AC: 1642 AN: 2114

Alfa AF: 0.810 Hom.: 29964

Bravo AF: 0.740

Asia WGS AF: 0.757 AC: 2631 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	0.98
DANN	Benign	0.56
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs10089685; hg19: chr8-55431353;