rs374987431

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1

The NM_006744.4(RBP4):c.558C>T(p.Ile186Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000683 in 1,611,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

RBP4
NM_006744.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.384

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 10-93593833-G-A is Benign according to our data. Variant chr10-93593833-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2162227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.384 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000046 (7/152170) while in subpopulation NFE AF = 0.000103 (7/68030). AF 95% confidence interval is 0.0000476. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBP4	NM_006744.4 link	c.558C>T	p.Ile186Ile	synonymous_variant	Exon 5 of 6	ENST00000371464.8	NP_006735.2	P02753
RBP4	NM_001323517.1 link	c.558C>T	p.Ile186Ile	synonymous_variant	Exon 5 of 6		NP_001310446.1	P02753
RBP4	NM_001323518.2 link	c.552C>T	p.Ile184Ile	synonymous_variant	Exon 5 of 6		NP_001310447.1	P02753Q5VY30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBP4	ENST00000371464.8 link	c.558C>T	p.Ile186Ile	synonymous_variant	Exon 5 of 6	1	NM_006744.4	ENSP00000360519.3	P02753
RBP4	ENST00000371467.5 link	c.558C>T	p.Ile186Ile	synonymous_variant	Exon 5 of 6	5		ENSP00000360522.1	P02753
RBP4	ENST00000371469.2 link	c.552C>T	p.Ile184Ile	synonymous_variant	Exon 5 of 6	5		ENSP00000360524.2	Q5VY30
FFAR4	ENST00000604414.1 link	c.697-10241G>A		intron_variant	Intron 2 of 2	3		ENSP00000474477.1	S4R3L2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000678

AC:

AN:

250642

AF XY:

0.0000664

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000706

AC:

103

AN:

1459420

Hom.:

Cov.:

AF XY:

0.0000730

AC XY:

AN XY:

726054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33416

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4348

European-Non Finnish (NFE)

AF:

0.0000908

AC:

101

AN:

1111834

Other (OTH)

AF:

0.0000166

AC:

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000378

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RBP4: BP4, BP7 -

Nov 23, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.2

(source)

DANN

Benign

0.73

PhyloP100

-0.38

Mutation Taster

=96/4

polymorphism

(source)

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

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rs374987431

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over