rs34812400

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006744.4(RBP4):c.381A>G(p.Thr127Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0081 in 1,613,704 control chromosomes in the GnomAD database, including 694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 361 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 333 hom. )

Consequence

RBP4
NM_006744.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.01

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 10-93594010-T-C is Benign according to our data. Variant chr10-93594010-T-C is described in ClinVar as Benign. ClinVar VariationId is 1167102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBP4	NM_006744.4 link	c.381A>G	p.Thr127Thr	synonymous_variant	Exon 5 of 6	ENST00000371464.8	NP_006735.2	P02753
RBP4	NM_001323517.1 link	c.381A>G	p.Thr127Thr	synonymous_variant	Exon 5 of 6		NP_001310446.1	P02753
RBP4	NM_001323518.2 link	c.375A>G	p.Thr125Thr	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.381A>G	p.Thr127Thr	synonymous_variant	Exon 5 of 6	1	NM_006744.4	ENSP00000360519.3	P02753
RBP4	ENST00000371467.5 link	c.381A>G	p.Thr127Thr	synonymous_variant	Exon 5 of 6	5		ENSP00000360522.1	P02753
RBP4	ENST00000371469.2 link	c.375A>G	p.Thr125Thr	synonymous_variant	Exon 5 of 6	5		ENSP00000360524.2	Q5VY30
FFAR4	ENST00000604414.1 link	c.697-10064T>C		intron_variant	Intron 2 of 2	3		ENSP00000474477.1	S4R3L2

Frequencies

GnomAD3 genomes

AF:

0.0395

AC:

6017

AN:

152138

Hom.:

361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0209

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.0330

GnomAD2 exomes

AF:

0.0112

AC:

2790

AN:

248602

AF XY:

0.00873

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.00924

Gnomad ASJ exome

AF:

0.00970

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00837

GnomAD4 exome

AF:

0.00482

AC:

7041

AN:

1461448

Hom.:

333

Cov.:

AF XY:

0.00430

AC XY:

3126

AN XY:

727030

show subpopulations

African (AFR)

AF:

0.138

AC:

4630

AN:

33478

American (AMR)

AF:

0.0105

AC:

470

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00926

AC:

242

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000290

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52988

Middle Eastern (MID)

AF:

0.0144

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000799

AC:

889

AN:

1112006

Other (OTH)

AF:

0.0116

AC:

701

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

415

831

1246

1662

2077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0396

AC:

6025

AN:

152256

Hom.:

361

Cov.:

AF XY:

0.0386

AC XY:

2877

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.133

AC:

5523

AN:

41534

American (AMR)

AF:

0.0209

AC:

319

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00104

AC:

AN:

68028

Other (OTH)

AF:

0.0326

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

272

544

815

1087

1359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0223

Hom.:

142

Bravo

AF:

0.0451

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00136

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 06, 2021

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.55

(source)

DANN

Benign

0.68

PhyloP100

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=92/8

polymorphism (auto)

(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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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