rs11187545

chr10-93597348-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006744.4(RBP4):c.355+3045T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,300 control chromosomes in the GnomAD database, including 730 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 0.087 (730 hom., cov: 32)
• Consequence: RBP4 NM_006744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBP4	NM_006744.4	c.355+3045T>C		intron_variant		ENST00000371464.8
RBP4	NM_001323517.1	c.355+3045T>C		intron_variant
RBP4	NM_001323518.2	c.349+3045T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBP4	ENST00000371464.8	c.355+3045T>C		intron_variant		1	NM_006744.4	P1
RBP4	ENST00000371467.5	c.355+3045T>C		intron_variant		5		P1
RBP4	ENST00000371469.2	c.349+3045T>C		intron_variant		5
FFAR4	ENST00000604414.1	c.697-6726A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0873 AC: 13289 AN: 152182 Hom.: 728 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.0907

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

GnomAD4 genome AF: 0.0874 AC: 13308 AN: 152300 Hom.: 730 Cov.: 32 AF XY: 0.0852 AC XY: 6347 AN XY: 74474

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0617

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0429

Gnomad4 FIN AF: 0.0739

Gnomad4 NFE AF: 0.0793

Gnomad4 OTH AF: 0.0898

Alfa AF: 0.0802 Hom.: 822

Bravo AF: 0.0878

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.6
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs11187545; hg19: chr10-95357105;