rs111245635

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_002900.3(RBP3):c.1037G>A(p.Arg346His) variant causes a missense change. The variant allele was found at a frequency of 0.0122 in 1,612,944 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 7 hom., cov: 33)

Exomes 𝑓: 0.013 ( 140 hom. )

Consequence

RBP3
NM_002900.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:7

Conservation

PhyloP100: 4.25

Variant links:

Genes affected

RBP3 (HGNC:9921): (retinol binding protein 3) Interphotoreceptor retinol-binding protein is a large glycoprotein known to bind retinoids and found primarily in the interphotoreceptor matrix of the retina between the retinal pigment epithelium and the photoreceptor cells. It is thought to transport retinoids between the retinal pigment epithelium and the photoreceptors, a critical role in the visual process.The human IRBP gene is approximately 9.5 kbp in length and consists of four exons separated by three introns. The introns are 1.6-1.9 kbp long. The gene is transcribed by photoreceptor and retinoblastoma cells into an approximately 4.3-kilobase mRNA that is translated and processed into a glycosylated protein of 135,000 Da. The amino acid sequence of human IRBP can be divided into four contiguous homology domains with 33-38% identity, suggesting a series of gene duplication events. In the gene, the boundaries of these domains are not defined by exon-intron junctions, as might have been expected. The first three homology domains and part of the fourth are all encoded by the first large exon, which is 3,180 base pairs long. The remainder of the fourth domain is encoded in the last three exons, which are 191, 143, and approximately 740 base pairs long, respectively. [provided by RefSeq, Jul 2008]

RBP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.085944325).

BP6

Variant 10-47349521-G-A is Benign according to our data. Variant chr10-47349521-G-A is described in ClinVar as [Benign]. Clinvar id is 208300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-47349521-G-A is described in Lovd as [Likely_benign]. Variant chr10-47349521-G-A is described in Lovd as [Benign]. Variant chr10-47349521-G-A is described in Lovd as [Likely_pathogenic].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00762 (1160/152260) while in subpopulation NFE AF= 0.0137 (931/68008). AF 95% confidence interval is 0.013. There are 7 homozygotes in gnomad4. There are 528 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBP3	NM_002900.3 link	c.1037G>A	p.Arg346His	missense_variant	Exon 1 of 4	ENST00000584701.2	NP_002891.1	P10745

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBP3	ENST00000584701.2 link	c.1037G>A	p.Arg346His	missense_variant	Exon 1 of 4	1	NM_002900.3	ENSP00000463151.1		P10745

Frequencies

GnomAD3 genomes

AF:

0.00762

AC:

1160

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00523

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00735

AC:

1830

AN:

248946

Hom.:

AF XY:

0.00752

AC XY:

1016

AN XY:

135092

show subpopulations

Gnomad AFR exome

AF:

0.00217

Gnomad AMR exome

AF:

0.00434

Gnomad ASJ exome

AF:

0.000898

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00414

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.00867

GnomAD4 exome

AF:

0.0127

AC:

18578

AN:

1460684

Hom.:

140

Cov.:

AF XY:

0.0124

AC XY:

9001

AN XY:

726640

show subpopulations

Gnomad4 AFR exome

AF:

0.00260

Gnomad4 AMR exome

AF:

0.00505

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.00165

Gnomad4 FIN exome

AF:

0.00498

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.00762

AC:

1160

AN:

152260

Hom.:

Cov.:

AF XY:

0.00709

AC XY:

528

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.00776

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RBP3: BS1, BS2 -

not specified

Benign:2

May 04, 2022

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Retinitis pigmentosa 66

Uncertain:1

Jun 27, 2013

ClinVar Staff, National Center for Biotechnology Information (NCBI)

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Retinitis pigmentosa

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_noAF

Pathogenic

0.40

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.28

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.086

Sift4G

Uncertain

0.0070

Vest4

0.66

gMVP

0.90

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over