Variant rs794726862 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate

The NM_006744.4(RBP4):c.217G>A(p.Ala73Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RBP4
NM_006744.4 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 7.54

Variant links:

Genes affected

RBP4 (HGNC:9922): (retinol binding protein 4) This protein belongs to the lipocalin family and is the specific carrier for retinol (vitamin A alcohol) in the blood. It delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin which prevents its loss by filtration through the kidney glomeruli. A deficiency of vitamin A blocks secretion of the binding protein posttranslationally and results in defective delivery and supply to the epidermal cells. [provided by RefSeq, Jul 2008]

RBP4 links:

FFAR4 (HGNC:19061): (free fatty acid receptor 4) This gene encodes a G protein-coupled receptor (GPR) which belongs to the rhodopsin family of GPRs. The encoded protein functions as a receptor for free fatty acids, including omega-3, and participates in suppressing anti-inflammatory responses and insulin sensitizing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

FFAR4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.891

PP5

Variant 10-93600698-C-T is Pathogenic according to our data. Variant chr10-93600698-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 192377.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RBP4	NM_006744.4 linkuse as main transcript	c.217G>A	p.Ala73Thr	missense_variant	3/6	ENST00000371464.8	NP_006735.2
RBP4	NM_001323517.1 linkuse as main transcript	c.217G>A	p.Ala73Thr	missense_variant	3/6		NP_001310446.1
RBP4	NM_001323518.2 linkuse as main transcript	c.211G>A	p.Ala71Thr	missense_variant	3/6		NP_001310447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RBP4	ENST00000371464.8 linkuse as main transcript	c.217G>A	p.Ala73Thr	missense_variant	3/6	1	NM_006744.4	ENSP00000360519	P1
RBP4	ENST00000371467.5 linkuse as main transcript	c.217G>A	p.Ala73Thr	missense_variant	3/6	5		ENSP00000360522	P1
RBP4	ENST00000371469.2 linkuse as main transcript	c.211G>A	p.Ala71Thr	missense_variant	3/6	5		ENSP00000360524
FFAR4	ENST00000604414.1 linkuse as main transcript	c.697-3376C>T		intron_variant		3		ENSP00000474477

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458298

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725142

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Bilateral microphthalmos

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Genetics Department, University Hospital of Toulouse

Dec 06, 2022

PS1, PM1, PM2, PP2, PP3 -

Microphthalmia, isolated, with coloboma 10

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 23, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

T;T;T;T

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

.;D;D;.

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.89

D;D;D;D

MetaSVM

Uncertain

0.60

MutationAssessor

Uncertain

2.2

M;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

N;N;.;N

REVEL

Pathogenic

0.74

Sift

Uncertain

0.012

D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.94

MutPred

0.75

Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);.;.;

MVP

0.63

MPC

1.6

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.82

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