10-93602293-T-G

Variant names:

• chr10-93602293-T-G
• rs3758538
• ENST00000854001.1:c.-242A>C

Variant summary

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

The ENST00000854001.1(RBP4):​c.-242A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,106 control chromosomes in the GnomAD database, including 2,837 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 0.18 (2837 hom., cov: 33)
• Consequence: RBP4 ENST00000854001.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864
• Publications: 15 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000854001.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP4	ENST00000854001.1		c.-242A>C		5_prime_UTR	Exon 2 of 8	ENSP00000524060.1
	RBP4	ENST00000854004.1		c.-242A>C		5_prime_UTR	Exon 2 of 8	ENSP00000524063.1
	RBP4	ENST00000854005.1		c.-242A>C		5_prime_UTR	Exon 1 of 7	ENSP00000524064.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27700 AN: 151988 Hom.: 2828 Cov.: 33

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.182 AC: 27734 AN: 152106 Hom.: 2837 Cov.: 33 AF XY: 0.177 AC XY: 13163 AN XY: 74360

African (AFR) AF: 0.277 AC: 11497 AN: 41490

American (AMR) AF: 0.153 AC: 2335 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 581 AN: 3470

East Asian (EAS) AF: 0.0628 AC: 325 AN: 5174

South Asian (SAS) AF: 0.184 AC: 887 AN: 4820

European-Finnish (FIN) AF: 0.0939 AC: 994 AN: 10584

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10443 AN: 67974

Other (OTH) AF: 0.172 AC: 363 AN: 2114

Alfa AF: 0.165 Hom.: 4073

Bravo AF: 0.189

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.35
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3758538; hg19: chr10-95362050;