ENST00000604414.1:c.697-12521A>G

Variant names:

• chr10-93591553-A-G
• rs34571439
• ENST00000604414.1:c.697-12521A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 12 publications found

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]

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

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000604414.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP4	NM_006744.4	MANE Select	c.*522T>C		downstream_gene	N/A	NP_006735.2
	RBP4	NM_001323518.2		c.*522T>C		downstream_gene	N/A	NP_001310447.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR4	ENST00000604414.1	TSL:3	c.697-12521A>G		intron	N/A	ENSP00000474477.1
	RBP4	ENST00000371464.8	TSL:1 MANE Select	c.*522T>C		downstream_gene	N/A	ENSP00000360519.3
	RBP4	ENST00000371467.5	TSL:5	c.*522T>C		downstream_gene	N/A	ENSP00000360522.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 5202 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2838

African (AFR) AF: 0.00 AC: 0 AN: 22

American (AMR) AF: 0.00 AC: 0 AN: 1042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20

East Asian (EAS) AF: 0.00 AC: 0 AN: 228

South Asian (SAS) AF: 0.00 AC: 0 AN: 416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 56

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 3208

Other (OTH) AF: 0.00 AC: 0 AN: 206

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3849

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.80
DANN	Benign	0.47
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs34571439; hg19: chr10-95351310;