rs76999824

Variant names:

• chr10-93592193-A-G
• rs76999824
• NM_006744.4:c.569-81T>C

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.569-81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00953 in 1,208,174 control chromosomes in the GnomAD database, including 613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (360 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (253 hom.)
• Consequence: RBP4 NM_006744.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.492
• Publications: 0 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=-0.89).
• BP6: Variant 10-93592193-A-G is Benign according to our data. Variant chr10-93592193-A-G is described in ClinVar as [Benign]. Clinvar id is 1263116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBP4	NM_006744.4	c.569-81T>C		intron_variant	Intron 5 of 5	ENST00000371464.8	NP_006735.2
RBP4	NM_001323517.1	c.569-81T>C		intron_variant	Intron 5 of 5		NP_001310446.1
RBP4	NM_001323518.2	c.563-81T>C		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.569-81T>C		intron_variant	Intron 5 of 5	1	NM_006744.4	ENSP00000360519.3
FFAR4	ENST00000604414.1	c.697-11881A>G		intron_variant	Intron 2 of 2	3		ENSP00000474477.1
RBP4	ENST00000371467.5	c.569-81T>C		intron_variant	Intron 5 of 5	5		ENSP00000360522.1
RBP4	ENST00000371469.2	c.563-81T>C		intron_variant	Intron 5 of 5	5		ENSP00000360524.2

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 6007 AN: 152230 Hom.: 360 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

GnomAD4 exome AF: 0.00521 AC: 5501 AN: 1055826 Hom.: 253 AF XY: 0.00455 AC XY: 2478 AN XY: 544178

African (AFR) AF: 0.138 AC: 3512 AN: 25516

American (AMR) AF: 0.0106 AC: 463 AN: 43676

Ashkenazi Jewish (ASJ) AF: 0.00936 AC: 220 AN: 23514

East Asian (EAS) AF: 0.00 AC: 0 AN: 37736

South Asian (SAS) AF: 0.000309 AC: 24 AN: 77654

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52760

Middle Eastern (MID) AF: 0.0142 AC: 71 AN: 5010

European-Non Finnish (NFE) AF: 0.000846 AC: 628 AN: 742712

Other (OTH) AF: 0.0123 AC: 582 AN: 47248

GnomAD4 genome AF: 0.0395 AC: 6015 AN: 152348 Hom.: 360 Cov.: 32 AF XY: 0.0385 AC XY: 2872 AN XY: 74514

African (AFR) AF: 0.133 AC: 5513 AN: 41556

American (AMR) AF: 0.0208 AC: 319 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00104 AC: 71 AN: 68042

Other (OTH) AF: 0.0326 AC: 69 AN: 2116

Alfa AF: 0.0630 Hom.: 201

Bravo AF: 0.0450

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 25, 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	-0.89
CADD	Benign	0.58
DANN	Benign	0.58
PhyloP100		-0.49
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: rs76999824; hg19: chr10-95351950;