ENST00000604414.1:c.697-2243C>T

Variant names:

• chr10-93601831-C-T
• rs3758539
• ENST00000604414.1:c.697-2243C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000604414.1(FFAR4):​c.697-2243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 571,988 control chromosomes in the GnomAD database, including 8,772 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 0.14 (1680 hom., cov: 33)
  • Exomes 𝑓: 0.17 (7092 hom.)
• Consequence: FFAR4 ENST00000604414.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 30 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: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
• microphthalmia, isolated, with coloboma 10

  Inheritance: AD, AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• isolated anophthalmia-microphthalmia syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP4	NM_001323518.2		c.-115G>A		upstream_gene	N/A	NP_001310447.1	Q5VY30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR4	ENST00000604414.1	TSL:3	c.697-2243C>T		intron	N/A	ENSP00000474477.1	S4R3L2
	RBP4	ENST00000854001.1		c.-19+121G>A		intron	N/A	ENSP00000524060.1
	RBP4	ENST00000854004.1		c.-19+121G>A		intron	N/A	ENSP00000524063.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20767 AN: 152062 Hom.: 1681 Cov.: 33

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.0957

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.170 AC: 71326 AN: 419808 Hom.: 7092 AF XY: 0.179 AC XY: 40803 AN XY: 227394

African (AFR) AF: 0.0717 AC: 757 AN: 10564

American (AMR) AF: 0.126 AC: 3075 AN: 24460

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 3388 AN: 14434

East Asian (EAS) AF: 0.0844 AC: 2059 AN: 24384

South Asian (SAS) AF: 0.308 AC: 14011 AN: 45560

European-Finnish (FIN) AF: 0.103 AC: 3122 AN: 30254

Middle Eastern (MID) AF: 0.212 AC: 600 AN: 2824

European-Non Finnish (NFE) AF: 0.165 AC: 40412 AN: 244220

Other (OTH) AF: 0.169 AC: 3902 AN: 23108

GnomAD4 genome AF: 0.137 AC: 20793 AN: 152180 Hom.: 1680 Cov.: 33 AF XY: 0.139 AC XY: 10318 AN XY: 74396

African (AFR) AF: 0.0684 AC: 2842 AN: 41542

American (AMR) AF: 0.151 AC: 2311 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3470

East Asian (EAS) AF: 0.0914 AC: 473 AN: 5174

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4814

European-Finnish (FIN) AF: 0.0957 AC: 1012 AN: 10580

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11259 AN: 67986

Other (OTH) AF: 0.176 AC: 372 AN: 2114

Alfa AF: 0.148 Hom.: 552

Bravo AF: 0.134

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Benign	0.90
PhyloP100		0.15
PromoterAI		-0.053	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3758539; hg19: chr10-95361588; COSMIC: COSV65160524; COSMIC: COSV65160524;