Variant rs137853290 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong

The NM_000326.5(RLBP1):c.452G>C(p.Arg151Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R151Q) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

RLBP1
NM_000326.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.35

Variant links:

Genes affected

RLBP1 (HGNC:10024): (retinaldehyde binding protein 1) The protein encoded by this gene is a 36-kD water-soluble protein which carries 11-cis-retinaldehyde or 11-cis-retinal as physiologic ligands. It may be a functional component of the visual cycle. Mutations of this gene have been associated with severe rod-cone dystrophy, Bothnia dystrophy (nonsyndromic autosomal recessive retinitis pigmentosa) and retinitis punctata albescens. [provided by RefSeq, Jul 2008]

RLBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PM1

In a domain CRAL-TRIO (size 161) in uniprot entity RLBP1_HUMAN there are 17 pathogenic changes around while only 1 benign (94%) in NM_000326.5

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr15-89215133-C-T is described in Lovd as [Pathogenic].

PP3

MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RLBP1	NM_000326.5 linkuse as main transcript	c.452G>C	p.Arg151Pro	missense_variant	6/9	ENST00000268125.10	NP_000317.1
RLBP1	XM_011521870.3 linkuse as main transcript	c.452G>C	p.Arg151Pro	missense_variant	6/9		XP_011520172.1
RLBP1	XM_047432927.1 linkuse as main transcript	c.452G>C	p.Arg151Pro	missense_variant	4/7		XP_047288883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RLBP1	ENST00000268125.10 linkuse as main transcript	c.452G>C	p.Arg151Pro	missense_variant	6/9	1	NM_000326.5	ENSP00000268125	P1
RLBP1	ENST00000567787.1 linkuse as main transcript	c.*30G>C		3_prime_UTR_variant, NMD_transcript_variant	6/8	5		ENSP00000457251

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251492

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.80

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.96

MetaSVM

Uncertain

0.13

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.6

REVEL

Pathogenic

0.75

Sift

Benign

0.10

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.97

MutPred

0.83

Loss of stability (P = 0.0217);

MVP

0.83

MPC

1.0

ClinPred

0.98

GERP RS

3.9

Varity_R

0.93

gMVP

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over