NM_006269.2:c.-13+311C>T

Variant names:

• chr8-54616513-C-T
• rs9643828
• NM_006269.2:c.-13+311C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006269.2. 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_006269.2	MANE Select	c.-13+311C>T		intron	N/A	NP_006260.1
	RP1	NM_001375654.1		c.-12-4442C>T		intron	N/A	NP_001362583.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RP1	ENST00000220676.2	TSL:1 MANE Select	c.-13+311C>T		intron	N/A	ENSP00000220676.1
	RP1	ENST00000637698.1	TSL:5	c.-13+311C>T		intron	N/A	ENSP00000490104.1
	RP1	ENST00000636932.1	TSL:5	c.-12-4442C>T		intron	N/A	ENSP00000489857.1

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

African (AFR) AF: 0.735 AC: 30481 AN: 41484

American (AMR) AF: 0.742 AC: 11336 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2777 AN: 3468

East Asian (EAS) AF: 0.724 AC: 3750 AN: 5176

South Asian (SAS) AF: 0.627 AC: 3028 AN: 4826

European-Finnish (FIN) AF: 0.639 AC: 6737 AN: 10538

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47303 AN: 67966

Other (OTH) AF: 0.755 AC: 1595 AN: 2112

Alfa AF: 0.718 Hom.: 50640

Bravo AF: 0.721

Asia WGS AF: 0.659 AC: 2290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.4
DANN	Benign	0.20
PhyloP100		0.96
PromoterAI		-0.010	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9643828; hg19: chr8-55529073;