Genetic Variant FFAR4:c.697-12521A>G (chr10-93591553-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000604414.1(FFAR4):c.697-12521A>G 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

FFAR4
ENST00000604414.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.14

Publications

12 publications found

Variant links:

Genes affected

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]

FFAR4 links:

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]

RBP4 Gene-Disease associations (from GenCC):

progressive retinal dystrophy due to retinol transport defect
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
microphthalmia, isolated, with coloboma
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet
microphthalmia, isolated, with coloboma 10
Inheritance: AD, AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
isolated anophthalmia-microphthalmia syndrome
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

RBP4 links:

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ACMG classification

Classification was made for transcript

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=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBP4	NM_006744.4 link	c.*522T>C		downstream_gene_variant		ENST00000371464.8	NP_006735.2
RBP4	NM_001323518.2 link	c.*522T>C		downstream_gene_variant			NP_001310447.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
FFAR4	ENST00000604414.1 link	c.697-12521A>G	intron_variant	Intron 2 of 2	3		ENSP00000474477.1
RBP4	ENST00000371464.8 link	c.*522T>C	downstream_gene_variant		1	NM_006744.4	ENSP00000360519.3
RBP4	ENST00000371467.5 link	c.*522T>C	downstream_gene_variant		5		ENSP00000360522.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

5202

Hom.:

AF XY:

0.00

AC XY:

AN XY:

2838

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

1042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

228

South Asian (SAS)

AF:

0.00

AC:

AN:

416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

3208

Other (OTH)

AF:

0.00

AC:

AN:

206

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

3849

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.80

(source)

DANN

Benign

0.47

PhyloP100

-2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over