rs17108991

Variant names:

• chr10-93593226-A-C
• rs17108991
• NM_006744.4:c.568+597T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006744.4(RBP4):​c.568+597T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,152 control chromosomes in the GnomAD database, including 2,765 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2765 hom., cov: 32)
• Consequence: RBP4 NM_006744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.980
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBP4	NM_006744.4	c.568+597T>G		intron_variant	Intron 5 of 5	ENST00000371464.8	NP_006735.2
RBP4	NM_001323517.1	c.568+597T>G		intron_variant	Intron 5 of 5		NP_001310446.1
RBP4	NM_001323518.2	c.562+597T>G		intron_variant	Intron 5 of 5		NP_001310447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBP4	ENST00000371464.8	c.568+597T>G		intron_variant	Intron 5 of 5	1	NM_006744.4	ENSP00000360519.3
FFAR4	ENST00000604414.1	c.697-10848A>C		intron_variant	Intron 2 of 2	3		ENSP00000474477.1
RBP4	ENST00000371467.5	c.568+597T>G		intron_variant	Intron 5 of 5	5		ENSP00000360522.1
RBP4	ENST00000371469.2	c.562+597T>G		intron_variant	Intron 5 of 5	5		ENSP00000360524.2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28375 AN: 152036 Hom.: 2760 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.106

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: 0.187 AC: 28425 AN: 152152 Hom.: 2765 Cov.: 32 AF XY: 0.190 AC XY: 14165 AN XY: 74372

African (AFR) AF: 0.209 AC: 8682 AN: 41520

American (AMR) AF: 0.172 AC: 2631 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3470

East Asian (EAS) AF: 0.107 AC: 553 AN: 5170

South Asian (SAS) AF: 0.339 AC: 1637 AN: 4822

European-Finnish (FIN) AF: 0.160 AC: 1697 AN: 10578

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11810 AN: 67994

Other (OTH) AF: 0.212 AC: 448 AN: 2114

Alfa AF: 0.180 Hom.: 9858

Bravo AF: 0.187

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.65
PhyloP100		0.98
Mutation Taster		=100/0	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: rs17108991; hg19: chr10-95352983;