rs7833405

Variant names:

• chr8-54576618-C-T
• rs7833405
• NM_001375654.1:c.-13+17298C>T

Variant summary

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

The NM_001375654.1(RP1):​c.-13+17298C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,082 control chromosomes in the GnomAD database, including 3,969 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 0.22 (3969 hom., cov: 33)
• Consequence: RP1 NM_001375654.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.661
• Publications: 0 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375654.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RP1	NM_001375654.1		c.-13+17298C>T		intron	N/A	NP_001362583.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RP1	ENST00000636932.1	TSL:5	c.-13+17298C>T		intron	N/A	ENSP00000489857.1
	RP1	ENST00000602362.2	TSL:2	n.836-421C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33771 AN: 151966 Hom.: 3968 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.222 AC: 33798 AN: 152082 Hom.: 3969 Cov.: 33 AF XY: 0.222 AC XY: 16481 AN XY: 74326

African (AFR) AF: 0.158 AC: 6571 AN: 41468

American (AMR) AF: 0.268 AC: 4093 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3464

East Asian (EAS) AF: 0.360 AC: 1860 AN: 5166

South Asian (SAS) AF: 0.147 AC: 708 AN: 4816

European-Finnish (FIN) AF: 0.235 AC: 2487 AN: 10574

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16386 AN: 67998

Other (OTH) AF: 0.245 AC: 517 AN: 2112

Alfa AF: 0.229 Hom.: 1586

Bravo AF: 0.228

Asia WGS AF: 0.246 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.54
PhyloP100		0.66

Splicing

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

Other links and lift over

dbSNP: rs7833405; hg19: chr8-55489178;