10-93592193-A-G

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.569-81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00953 in 1,208,174 control chromosomes in the GnomAD database, including 613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (360 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (253 hom.)
• Consequence: RBP4 NM_006744.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.492

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=-0.89).
• BP6: Variant 10-93592193-A-G is Benign according to our data. Variant chr10-93592193-A-G is described in ClinVar as [Benign]. Clinvar id is 1263116.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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/exons	MANE	UniProt
RBP4	NM_006744.4	c.569-81T>C		intron_variant		ENST00000371464.8
RBP4	NM_001323517.1	c.569-81T>C		intron_variant
RBP4	NM_001323518.2	c.563-81T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBP4	ENST00000371464.8	c.569-81T>C		intron_variant		1	NM_006744.4	P1
RBP4	ENST00000371467.5	c.569-81T>C		intron_variant		5		P1
RBP4	ENST00000371469.2	c.563-81T>C		intron_variant		5
FFAR4	ENST00000604414.1	c.697-11881A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 6007 AN: 152230 Hom.: 360 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

GnomAD4 exome AF: 0.00521 AC: 5501 AN: 1055826 Hom.: 253 AF XY: 0.00455 AC XY: 2478 AN XY: 544178

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.00936

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000309

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.000846

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.0395 AC: 6015 AN: 152348 Hom.: 360 Cov.: 32 AF XY: 0.0385 AC XY: 2872 AN XY: 74514

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0337 Hom.: 30

Bravo AF: 0.0450

Asia WGS AF: 0.00751 AC: 26 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 25, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.58
Dann	Benign	0.58

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: rs76999824; hg19: chr10-95351950;