NM_006744.4:c.-55T>G

Variant names:

• chr10-93601207-A-C
• rs10882283
• NM_006744.4:c.-55T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.969
• Publications: 23 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 -20 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 VariationId is 1260386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP4	NM_006744.4	MANE Select	c.-55T>G		5_prime_UTR	Exon 1 of 6	NP_006735.2
	RBP4	NM_001323517.1		c.-19+155T>G		intron	N/A	NP_001310446.1
	RBP4	NM_001323518.2		c.52-236T>G		intron	N/A	NP_001310447.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP4	ENST00000371464.8	TSL:1 MANE Select	c.-55T>G		5_prime_UTR	Exon 1 of 6	ENSP00000360519.3
	FFAR4	ENST00000604414.1	TSL:3	c.697-2867A>C		intron	N/A	ENSP00000474477.1
	RBP4	ENST00000371467.5	TSL:5	c.-19+155T>G		intron	N/A	ENSP00000360522.1

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

African (AFR) AF: 0.408 AC: 9191 AN: 22528

American (AMR) AF: 0.259 AC: 2233 AN: 8618

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 6446 AN: 14946

East Asian (EAS) AF: 0.0921 AC: 2403 AN: 26088

South Asian (SAS) AF: 0.372 AC: 15307 AN: 41134

European-Finnish (FIN) AF: 0.331 AC: 8963 AN: 27044

Middle Eastern (MID) AF: 0.456 AC: 1425 AN: 3122

European-Non Finnish (NFE) AF: 0.381 AC: 370106 AN: 971040

Other (OTH) AF: 0.380 AC: 17926 AN: 47156

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

African (AFR) AF: 0.411 AC: 16936 AN: 41180

American (AMR) AF: 0.313 AC: 4754 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1508 AN: 3452

East Asian (EAS) AF: 0.111 AC: 540 AN: 4850

South Asian (SAS) AF: 0.419 AC: 1986 AN: 4742

European-Finnish (FIN) AF: 0.353 AC: 3616 AN: 10234

Middle Eastern (MID) AF: 0.479 AC: 139 AN: 290

European-Non Finnish (NFE) AF: 0.388 AC: 26155 AN: 67468

Other (OTH) AF: 0.398 AC: 838 AN: 2106

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:2

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		-0.97
PromoterAI		0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs10882283; hg19: chr10-95360964;