rs36014035

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006744.4(RBP4):c.355+123T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 871,908 control chromosomes in the GnomAD database, including 64,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12240 hom., cov: 32)

Exomes 𝑓: 0.37 ( 52131 hom. )

Consequence

RBP4
NM_006744.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.833

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 10-93600270-A-C is Benign according to our data. Variant chr10-93600270-A-C is described in ClinVar as [Benign]. Clinvar id is 931422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RBP4	NM_006744.4 link	c.355+123T>G	intron_variant	Intron 4 of 5	ENST00000371464.8	NP_006735.2	P02753
RBP4	NM_001323517.1 link	c.355+123T>G	intron_variant	Intron 4 of 5		NP_001310446.1	P02753
RBP4	NM_001323518.2 link	c.349+123T>G	intron_variant	Intron 4 of 5		NP_001310447.1	P02753Q5VY30

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBP4	ENST00000371464.8 link	c.355+123T>G	intron_variant	Intron 4 of 5	1	NM_006744.4	ENSP00000360519.3	P02753
FFAR4	ENST00000604414.1 link	c.697-3804A>C	intron_variant	Intron 2 of 2	3		ENSP00000474477.1	S4R3L2
RBP4	ENST00000371467.5 link	c.355+123T>G	intron_variant	Intron 4 of 5	5		ENSP00000360522.1	P02753
RBP4	ENST00000371469.2 link	c.349+123T>G	intron_variant	Intron 4 of 5	5		ENSP00000360524.2	Q5VY30

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59712

AN:

151812

Hom.:

12215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.405

GnomAD4 exome

AF:

0.371

AC:

267137

AN:

719978

Hom.:

52131

AF XY:

0.376

AC XY:

144357

AN XY:

384082

show subpopulations

Gnomad4 AFR exome

AF:

0.475

Gnomad4 AMR exome

AF:

0.246

Gnomad4 ASJ exome

AF:

0.456

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.436

Gnomad4 FIN exome

AF:

0.343

Gnomad4 NFE exome

AF:

0.385

Gnomad4 OTH exome

AF:

0.390

GnomAD4 genome

AF:

0.394

AC:

59798

AN:

151930

Hom.:

12240

Cov.:

AF XY:

0.392

AC XY:

29101

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.477

Gnomad4 AMR

AF:

0.314

Gnomad4 ASJ

AF:

0.449

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.437

Gnomad4 FIN

AF:

0.343

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.401

Alfa

AF:

0.380

Hom.:

1382

Bravo

AF:

0.392

Asia WGS

AF:

0.277

AC:

963

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Progressive retinal dystrophy due to retinol transport defect

Benign:1

Dec 20, 2018

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was classified as: Benign. This variant was detected in homozygous state. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.6

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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