dbSNP rs34571439: FFAR4:c.697-12521A>C (chr10-93591553-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000604414.1(FFAR4):c.697-12521A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 157,126 control chromosomes in the GnomAD database, including 4,933 homozygotes. 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: 𝑓 0.24 ( 4848 hom., cov: 32)

Exomes 𝑓: 0.15 ( 85 hom. )

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBP4	NM_006744.4 link	c.*522T>G		downstream_gene_variant		ENST00000371464.8	NP_006735.2	P02753
RBP4	NM_001323518.2 link	c.*522T>G		downstream_gene_variant			NP_001310447.1	P02753Q5VY30

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FFAR4	ENST00000604414.1 link	c.697-12521A>C	intron_variant	Intron 2 of 2	3		ENSP00000474477.1	S4R3L2
RBP4	ENST00000371464.8 link	c.*522T>G	downstream_gene_variant		1	NM_006744.4	ENSP00000360519.3	P02753
RBP4	ENST00000371467.5 link	c.*522T>G	downstream_gene_variant		5		ENSP00000360522.1	P02753

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35859

AN:

151814

Hom.:

4836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.152

AC:

789

AN:

5194

Hom.:

AF XY:

0.146

AC XY:

414

AN XY:

2836

show subpopulations

African (AFR)

AF:

0.364

AC:

AN:

American (AMR)

AF:

0.164

AC:

171

AN:

1040

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

AN:

East Asian (EAS)

AF:

0.0833

AC:

AN:

228

South Asian (SAS)

AF:

0.250

AC:

104

AN:

416

European-Finnish (FIN)

AF:

0.0714

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.136

AC:

434

AN:

3202

Other (OTH)

AF:

0.184

AC:

AN:

206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.236

AC:

35922

AN:

151932

Hom.:

4848

Cov.:

AF XY:

0.238

AC XY:

17708

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.365

AC:

15116

AN:

41410

American (AMR)

AF:

0.200

AC:

3047

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

879

AN:

3466

East Asian (EAS)

AF:

0.107

AC:

554

AN:

5154

South Asian (SAS)

AF:

0.340

AC:

1634

AN:

4808

European-Finnish (FIN)

AF:

0.162

AC:

1713

AN:

10564

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.181

AC:

12307

AN:

67948

Other (OTH)

AF:

0.249

AC:

525

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1370

2740

4109

5479

6849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.198

Hom.:

3849

Bravo

AF:

0.242

Asia WGS

AF:

0.212

AC:

737

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.72

(source)

DANN

Benign

0.17

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over