10-93594010-T-C

Position:

• chr10-93594010-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006744.4(RBP4):​c.381A>G​(p.Thr127Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0081 in 1,613,704 control chromosomes in the GnomAD database, including 694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (361 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (333 hom.)
• Consequence: RBP4 NM_006744.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.01

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 10-93594010-T-C is Benign according to our data. Variant chr10-93594010-T-C is described in ClinVar as [Benign]. Clinvar id is 1167102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBP4	NM_006744.4	c.381A>G	p.Thr127Thr	synonymous_variant	5/6	ENST00000371464.8	NP_006735.2
RBP4	NM_001323517.1	c.381A>G	p.Thr127Thr	synonymous_variant	5/6		NP_001310446.1
RBP4	NM_001323518.2	c.375A>G	p.Thr125Thr	synonymous_variant	5/6		NP_001310447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBP4	ENST00000371464.8	c.381A>G	p.Thr127Thr	synonymous_variant	5/6	1	NM_006744.4	ENSP00000360519.3
RBP4	ENST00000371467.5	c.381A>G	p.Thr127Thr	synonymous_variant	5/6	5		ENSP00000360522.1
RBP4	ENST00000371469.2	c.375A>G	p.Thr125Thr	synonymous_variant	5/6	5		ENSP00000360524.2
FFAR4	ENST00000604414.1	c.697-10064T>C		intron_variant		3		ENSP00000474477.1

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 6017 AN: 152138 Hom.: 361 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.0330

GnomAD3 exomes AF: 0.0112 AC: 2790 AN: 248602 Hom.: 151 AF XY: 0.00873 AC XY: 1175 AN XY: 134564

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.00924

Gnomad ASJ exome AF: 0.00970

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000360

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00110

Gnomad OTH exome AF: 0.00837

GnomAD4 exome AF: 0.00482 AC: 7041 AN: 1461448 Hom.: 333 Cov.: 32 AF XY: 0.00430 AC XY: 3126 AN XY: 727030

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.00926

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000799

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome AF: 0.0396 AC: 6025 AN: 152256 Hom.: 361 Cov.: 32 AF XY: 0.0386 AC XY: 2877 AN XY: 74448

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0209

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0206 Hom.: 115

Bravo AF: 0.0451

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.00164

EpiControl AF: 0.00136

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.55
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs34812400; hg19: chr10-95353767;