10-93593756-G-A

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.568+67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 1,521,986 control chromosomes in the GnomAD database, including 5,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (410 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5242 hom.)
• Consequence: RBP4 NM_006744.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.939

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=-0.87).
• BP6: Variant 10-93593756-G-A is Benign according to our data. Variant chr10-93593756-G-A is described in ClinVar as [Benign]. Clinvar id is 1282263.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBP4	NM_006744.4	c.568+67C>T		intron_variant		ENST00000371464.8
RBP4	NM_001323517.1	c.568+67C>T		intron_variant
RBP4	NM_001323518.2	c.562+67C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBP4	ENST00000371464.8	c.568+67C>T		intron_variant		1	NM_006744.4	P1
RBP4	ENST00000371467.5	c.568+67C>T		intron_variant		5		P1
RBP4	ENST00000371469.2	c.562+67C>T		intron_variant		5
FFAR4	ENST00000604414.1	c.697-10318G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9203 AN: 152028 Hom.: 410 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.0502

GnomAD4 exome AF: 0.0817 AC: 111861 AN: 1369840 Hom.: 5242 AF XY: 0.0802 AC XY: 55097 AN XY: 686680

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0337

Gnomad4 ASJ exome AF: 0.0568

Gnomad4 EAS exome AF: 0.000280

Gnomad4 SAS exome AF: 0.0286

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0930

Gnomad4 OTH exome AF: 0.0754

GnomAD4 genome AF: 0.0605 AC: 9201 AN: 152146 Hom.: 410 Cov.: 32 AF XY: 0.0611 AC XY: 4545 AN XY: 74372

Gnomad4 AFR AF: 0.0160

Gnomad4 AMR AF: 0.0422

Gnomad4 ASJ AF: 0.0614

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0216

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0896

Gnomad4 OTH AF: 0.0488

Alfa AF: 0.0778 Hom.: 56

Bravo AF: 0.0535

Asia WGS AF: 0.0120 AC: 43 AN: 3478

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 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.095
Dann	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs76582050; hg19: chr10-95353513; COSMIC: COSV65160836; COSMIC: COSV65160836;