10-93600270-A-G

Variant names:

• chr10-93600270-A-G
• rs36014035
• NM_006744.4:c.355+123T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006744.4(RBP4):​c.355+123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBP4 NM_006744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833
• Publications: 11 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBP4	NM_006744.4	c.355+123T>C		intron_variant	Intron 4 of 5	ENST00000371464.8	NP_006735.2
RBP4	NM_001323517.1	c.355+123T>C		intron_variant	Intron 4 of 5		NP_001310446.1
RBP4	NM_001323518.2	c.349+123T>C		intron_variant	Intron 4 of 5		NP_001310447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBP4	ENST00000371464.8	c.355+123T>C		intron_variant	Intron 4 of 5	1	NM_006744.4	ENSP00000360519.3
FFAR4	ENST00000604414.1	c.697-3804A>G		intron_variant	Intron 2 of 2	3		ENSP00000474477.1
RBP4	ENST00000371467.5	c.355+123T>C		intron_variant	Intron 4 of 5	5		ENSP00000360522.1
RBP4	ENST00000371469.2	c.349+123T>C		intron_variant	Intron 4 of 5	5		ENSP00000360524.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 720984 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 384604

African (AFR) AF: 0.00 AC: 0 AN: 19216

American (AMR) AF: 0.00 AC: 0 AN: 40966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21206

East Asian (EAS) AF: 0.00 AC: 0 AN: 35522

South Asian (SAS) AF: 0.00 AC: 0 AN: 69272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4382

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 453410

Other (OTH) AF: 0.00 AC: 0 AN: 36294

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1382

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.71
PhyloP100		-0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs36014035; hg19: chr10-95360027;