10-93593756-G-A

Variant names:

• chr10-93593756-G-A
• rs76582050
• NM_006744.4:c.568+67C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006744.4(RBP4):​c.568+67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 1,521,986 control chromosomes in the GnomAD database, including 5,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (410 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5242 hom.)
• Consequence: RBP4 NM_006744.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.939
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-93593756-G-A is Benign according to our data. Variant chr10-93593756-G-A is described in ClinVar as [Benign]. Clinvar id is 1282263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBP4	NM_006744.4	c.568+67C>T		intron_variant	Intron 5 of 5	ENST00000371464.8	NP_006735.2
RBP4	NM_001323517.1	c.568+67C>T		intron_variant	Intron 5 of 5		NP_001310446.1
RBP4	NM_001323518.2	c.562+67C>T		intron_variant	Intron 5 of 5		NP_001310447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBP4	ENST00000371464.8	c.568+67C>T		intron_variant	Intron 5 of 5	1	NM_006744.4	ENSP00000360519.3
FFAR4	ENST00000604414.1	c.697-10318G>A		intron_variant	Intron 2 of 2	3		ENSP00000474477.1
RBP4	ENST00000371467.5	c.568+67C>T		intron_variant	Intron 5 of 5	5		ENSP00000360522.1
RBP4	ENST00000371469.2	c.562+67C>T		intron_variant	Intron 5 of 5	5		ENSP00000360524.2

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9203 AN: 152028 Hom.: 410 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.0502

GnomAD4 exome AF: 0.0817 AC: 111861 AN: 1369840 Hom.: 5242 AF XY: 0.0802 AC XY: 55097 AN XY: 686680

African (AFR) AF: 0.0116 AC: 368 AN: 31708

American (AMR) AF: 0.0337 AC: 1504 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 1457 AN: 25646

East Asian (EAS) AF: 0.000280 AC: 11 AN: 39334

South Asian (SAS) AF: 0.0286 AC: 2410 AN: 84392

European-Finnish (FIN) AF: 0.112 AC: 5183 AN: 46450

Middle Eastern (MID) AF: 0.0559 AC: 223 AN: 3992

European-Non Finnish (NFE) AF: 0.0930 AC: 96376 AN: 1036300

Other (OTH) AF: 0.0754 AC: 4329 AN: 57396

GnomAD4 genome AF: 0.0605 AC: 9201 AN: 152146 Hom.: 410 Cov.: 32 AF XY: 0.0611 AC XY: 4545 AN XY: 74372

African (AFR) AF: 0.0160 AC: 663 AN: 41512

American (AMR) AF: 0.0422 AC: 645 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3468

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5174

South Asian (SAS) AF: 0.0216 AC: 104 AN: 4814

European-Finnish (FIN) AF: 0.122 AC: 1295 AN: 10572

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0896 AC: 6091 AN: 68008

Other (OTH) AF: 0.0488 AC: 103 AN: 2112

Alfa AF: 0.0752 Hom.: 56

Bravo AF: 0.0535

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.095
DANN	Benign	0.67
PhyloP100		-0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs76582050; hg19: chr10-95353513; COSMIC: COSV65160836; COSMIC: COSV65160836;