rs34812400

Variant names:

• chr10-93594010-T-C
• rs34812400
• NM_006744.4:c.381A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.01
• Publications: 1 publications found

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]

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006744.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP4	NM_006744.4	MANE Select	c.381A>G	p.Thr127Thr	synonymous	Exon 5 of 6	NP_006735.2	P02753
	RBP4	NM_001323517.1		c.381A>G	p.Thr127Thr	synonymous	Exon 5 of 6	NP_001310446.1	P02753
	RBP4	NM_001323518.2		c.375A>G	p.Thr125Thr	synonymous	Exon 5 of 6	NP_001310447.1	Q5VY30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP4	ENST00000371464.8	TSL:1 MANE Select	c.381A>G	p.Thr127Thr	synonymous	Exon 5 of 6	ENSP00000360519.3	P02753
	RBP4	ENST00000854018.1		c.405A>G	p.Thr135Thr	synonymous	Exon 5 of 6	ENSP00000524077.1
	RBP4	ENST00000371467.5	TSL:5	c.381A>G	p.Thr127Thr	synonymous	Exon 5 of 6	ENSP00000360522.1	P02753

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 6017 AN: 152138 Hom.: 361 Cov.: 32

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

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.: 32 AF XY: 0.00430 AC XY: 3126 AN XY: 727030

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: 0 AN: 39700

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86258

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52988

Middle Eastern (MID) AF: 0.0144 AC: 83 AN: 5766

European-Non Finnish (NFE) AF: 0.000799 AC: 889 AN: 1112006

Other (OTH) AF: 0.0116 AC: 701 AN: 60392

GnomAD4 genome AF: 0.0396 AC: 6025 AN: 152256 Hom.: 361 Cov.: 32 AF XY: 0.0386 AC XY: 2877 AN XY: 74448

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: 37 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00104 AC: 71 AN: 68028

Other (OTH) AF: 0.0326 AC: 69 AN: 2116

Alfa AF: 0.0223 Hom.: 142

Bravo AF: 0.0451

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.00164

EpiControl AF: 0.00136

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.55
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)

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

Other links and lift over

dbSNP: rs34812400; hg19: chr10-95353767;