rs10882283

chr10-93601207-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006744.4(RBP4):c.-55T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,312,070 control chromosomes in the GnomAD database, including 94,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11010 hom., cov: 32)
  • Exomes 𝑓: 0.37 (83135 hom.)
• Consequence: RBP4 NM_006744.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.969

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-93601207-A-C is Benign according to our data. Variant chr10-93601207-A-C is described in ClinVar as [Benign]. Clinvar id is 1260386.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBP4	NM_006744.4	c.-55T>G		5_prime_UTR_variant	1/6	ENST00000371464.8
RBP4	NM_001323517.1	c.-19+155T>G		intron_variant
RBP4	NM_001323518.2	c.52-236T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBP4	ENST00000371464.8	c.-55T>G		5_prime_UTR_variant	1/6	1	NM_006744.4	P1
RBP4	ENST00000371467.5	c.-19+155T>G		intron_variant		5		P1
RBP4	ENST00000371469.2	c.52-236T>G		intron_variant		5
FFAR4	ENST00000604414.1	c.697-2867A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.377 AC: 56676 AN: 150270 Hom.: 10998 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.374 AC: 434000 AN: 1161676 Hom.: 83135 Cov.: 37 AF XY: 0.373 AC XY: 208872 AN XY: 559438

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.0921

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.381

Gnomad4 OTH exome AF: 0.380

GnomAD4 genome AF: 0.377 AC: 56728 AN: 150394 Hom.: 11010 Cov.: 32 AF XY: 0.377 AC XY: 27663 AN XY: 73466

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.398

Alfa AF: 0.380 Hom.: 1391

Bravo AF: 0.372

Asia WGS AF: 0.254 AC: 879 AN: 3452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	12
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs10882283; hg19: chr10-95360964;