10-93593485-CA-C

Position:

• chr10-93593485-CA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_006744.4(RBP4):​c.568+337del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,086 control chromosomes in the GnomAD database, including 2,755 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2755 hom., cov: 28)
• Consequence: RBP4 NM_006744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBP4	NM_006744.4	c.568+337del		intron_variant		ENST00000371464.8	NP_006735.2
RBP4	NM_001323517.1	c.568+337del		intron_variant			NP_001310446.1
RBP4	NM_001323518.2	c.562+337del		intron_variant			NP_001310447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBP4	ENST00000371464.8	c.568+337del		intron_variant		1	NM_006744.4	ENSP00000360519	P1
RBP4	ENST00000371467.5	c.568+337del		intron_variant		5		ENSP00000360522	P1
RBP4	ENST00000371469.2	c.562+337del		intron_variant		5		ENSP00000360524
FFAR4	ENST00000604414.1	c.697-10587del		intron_variant		3		ENSP00000474477

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28311 AN: 151968 Hom.: 2751 Cov.: 28

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.214

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.186 AC: 28361 AN: 152086 Hom.: 2755 Cov.: 28 AF XY: 0.190 AC XY: 14120 AN XY: 74316

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.213

Alfa AF: 0.173 Hom.: 306

Bravo AF: 0.186

Asia WGS AF: 0.201 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs36035572; hg19: chr10-95353242;