ENST00000637698.1:c.1324-504C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000637698.1(RP1):​c.1324-504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,070 control chromosomes in the GnomAD database, including 4,282 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 ( 4282 hom., cov: 33)

Consequence

RP1
ENST00000637698.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.265
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RP1NM_001375654.1 linkc.1324-504C>T intron_variant Intron 7 of 29 NP_001362583.1
RP1XM_047422069.1 linkc.1345-504C>T intron_variant Intron 8 of 29 XP_047278025.1
RP1XM_047422070.1 linkc.1345-504C>T intron_variant Intron 8 of 29 XP_047278026.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RP1ENST00000637698.1 linkc.1324-504C>T intron_variant Intron 7 of 28 5 ENSP00000490104.1 A0A1B0GUH0
RP1ENST00000636932.1 linkc.1324-504C>T intron_variant Intron 7 of 22 5 ENSP00000489857.1 A0A1B0GTV9

Frequencies

GnomAD3 genomes
AF:
0.220
AC:
33503
AN:
151950
Hom.:
4273
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0998
Gnomad AMI
AF:
0.212
Gnomad AMR
AF:
0.319
Gnomad ASJ
AF:
0.229
Gnomad EAS
AF:
0.423
Gnomad SAS
AF:
0.240
Gnomad FIN
AF:
0.206
Gnomad MID
AF:
0.272
Gnomad NFE
AF:
0.256
Gnomad OTH
AF:
0.252
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.221
AC:
33537
AN:
152070
Hom.:
4282
Cov.:
33
AF XY:
0.221
AC XY:
16414
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.100
Gnomad4 AMR
AF:
0.320
Gnomad4 ASJ
AF:
0.229
Gnomad4 EAS
AF:
0.423
Gnomad4 SAS
AF:
0.240
Gnomad4 FIN
AF:
0.206
Gnomad4 NFE
AF:
0.256
Gnomad4 OTH
AF:
0.254
Alfa
AF:
0.236
Hom.:
744
Bravo
AF:
0.225
Asia WGS
AF:
0.319
AC:
1109
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.1
DANN
Benign
0.54

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs453186; hg19: chr8-55585906; API