8-54871415-C-T

Variant names:

• chr8-54871415-C-T
• rs9298514
• ENST00000637698.1:c.*1473C>T

Variant summary

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

The ENST00000637698.1(RP1):​c.*1473C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,690 control chromosomes in the GnomAD database, including 3,620 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 0.21 (3620 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RP1 ENST00000637698.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RP1	NM_001375654.1	c.*1473C>T		downstream_gene_variant			NP_001362583.1
RP1	XM_047422069.1	c.*1473C>T		downstream_gene_variant			XP_047278025.1
RP1	XM_047422070.1	c.*1473C>T		downstream_gene_variant			XP_047278026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RP1	ENST00000637698.1	c.*1473C>T		3_prime_UTR_variant	Exon 29 of 29	5		ENSP00000490104.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31454 AN: 151574 Hom.: 3621 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.159

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 AFR exome AC: 0 AN: 0

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AC: 0 AN: 0

Gnomad4 SAS exome AC: 0 AN: 0

Gnomad4 FIN exome AC: 0 AN: 0

Gnomad4 NFE exome AF: 0.00 AC: 0 AN: 2

Gnomad4 Remaining exome AC: 0 AN: 0

GnomAD4 genome AF: 0.207 AC: 31459 AN: 151690 Hom.: 3620 Cov.: 31 AF XY: 0.212 AC XY: 15673 AN XY: 74098

Gnomad4 AFR AF: 0.275 AC: 0.275473 AN: 0.275473

Gnomad4 AMR AF: 0.151 AC: 0.151155 AN: 0.151155

Gnomad4 ASJ AF: 0.0625 AC: 0.0625 AN: 0.0625

Gnomad4 EAS AF: 0.435 AC: 0.434774 AN: 0.434774

Gnomad4 SAS AF: 0.336 AC: 0.336329 AN: 0.336329

Gnomad4 FIN AF: 0.214 AC: 0.213525 AN: 0.213525

Gnomad4 NFE AF: 0.163 AC: 0.162603 AN: 0.162603

Gnomad4 OTH AF: 0.157 AC: 0.156844 AN: 0.156844

Alfa AF: 0.167 Hom.: 3508

Bravo AF: 0.199

Asia WGS AF: 0.342 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9298514; hg19: chr8-55783975;