rs9643828

Positions:

• chr8-54616513-C-T

Variant summary

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

The NM_006269.2(RP1):​c.-13+311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,060 control chromosomes in the GnomAD database, including 38,310 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 0.71 (38310 hom., cov: 32)
• Consequence: RP1 NM_006269.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.961

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RP1	NM_006269.2	c.-13+311C>T		intron_variant		ENST00000220676.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RP1	ENST00000220676.2	c.-13+311C>T		intron_variant		1	NM_006269.2
RP1	ENST00000636932.1	c.-12-4442C>T		intron_variant		5
RP1	ENST00000637698.1	c.-13+311C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107669 AN: 151942 Hom.: 38263 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.709 AC: 107770 AN: 152060 Hom.: 38310 Cov.: 32 AF XY: 0.707 AC XY: 52546 AN XY: 74318

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.755

Alfa AF: 0.716 Hom.: 39513

Bravo AF: 0.721

Asia WGS AF: 0.659 AC: 2290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.4
DANN	Benign	0.20

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: rs9643828; hg19: chr8-55529073;