10-93600623-A-G

Position:

• chr10-93600623-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006744.4(RBP4):​c.248+44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 1,611,628 control chromosomes in the GnomAD database, including 4,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (616 hom., cov: 33)
  • Exomes 𝑓: 0.073 (4332 hom.)
• Consequence: RBP4 NM_006744.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.419

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-93600623-A-G is Benign according to our data. Variant chr10-93600623-A-G is described in ClinVar as [Benign]. Clinvar id is 1271228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBP4	NM_006744.4	c.248+44T>C		intron_variant		ENST00000371464.8	NP_006735.2
RBP4	NM_001323517.1	c.248+44T>C		intron_variant			NP_001310446.1
RBP4	NM_001323518.2	c.242+44T>C		intron_variant			NP_001310447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBP4	ENST00000371464.8	c.248+44T>C		intron_variant		1	NM_006744.4	ENSP00000360519	P1
RBP4	ENST00000371467.5	c.248+44T>C		intron_variant		5		ENSP00000360522	P1
RBP4	ENST00000371469.2	c.242+44T>C		intron_variant		5		ENSP00000360524
FFAR4	ENST00000604414.1	c.697-3451A>G		intron_variant		3		ENSP00000474477

Frequencies

GnomAD3 genomes AF: 0.0811 AC: 12341 AN: 152140 Hom.: 615 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0428

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0787

Gnomad OTH AF: 0.0871

GnomAD3 exomes AF: 0.0634 AC: 15445 AN: 243520 Hom.: 562 AF XY: 0.0638 AC XY: 8426 AN XY: 132146

Gnomad AFR exome AF: 0.0951

Gnomad AMR exome AF: 0.0380

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.00116

Gnomad SAS exome AF: 0.0461

Gnomad FIN exome AF: 0.0765

Gnomad NFE exome AF: 0.0746

Gnomad OTH exome AF: 0.0743

GnomAD4 exome AF: 0.0730 AC: 106595 AN: 1459370 Hom.: 4332 Cov.: 34 AF XY: 0.0728 AC XY: 52812 AN XY: 725828

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.0412

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.000882

Gnomad4 SAS exome AF: 0.0468

Gnomad4 FIN exome AF: 0.0746

Gnomad4 NFE exome AF: 0.0764

Gnomad4 OTH exome AF: 0.0780

GnomAD4 genome AF: 0.0812 AC: 12357 AN: 152258 Hom.: 616 Cov.: 33 AF XY: 0.0791 AC XY: 5888 AN XY: 74442

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0595

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0428

Gnomad4 FIN AF: 0.0743

Gnomad4 NFE AF: 0.0787

Gnomad4 OTH AF: 0.0862

Alfa AF: 0.0891 Hom.: 134

Bravo AF: 0.0802

Asia WGS AF: 0.0360 AC: 127 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs61461737; hg19: chr10-95360380;