10-93591553-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• 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: 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.

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>G		downstream_gene	N/A	NP_006735.2
	RBP4	NM_001323518.2		c.*522T>G		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>C		intron	N/A	ENSP00000474477.1
	RBP4	ENST00000371464.8	TSL:1 MANE Select	c.*522T>G		downstream_gene	N/A	ENSP00000360519.3
	RBP4	ENST00000371467.5	TSL:5	c.*522T>G		downstream_gene	N/A	ENSP00000360522.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35859 AN: 151814 Hom.: 4836 Cov.: 32

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.: 85 AF XY: 0.146 AC XY: 414 AN XY: 2836

African (AFR) AF: 0.364 AC: 8 AN: 22

American (AMR) AF: 0.164 AC: 171 AN: 1040

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 8 AN: 20

East Asian (EAS) AF: 0.0833 AC: 19 AN: 228

South Asian (SAS) AF: 0.250 AC: 104 AN: 416

European-Finnish (FIN) AF: 0.0714 AC: 4 AN: 56

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.136 AC: 434 AN: 3202

Other (OTH) AF: 0.184 AC: 38 AN: 206

GnomAD4 genome AF: 0.236 AC: 35922 AN: 151932 Hom.: 4848 Cov.: 32 AF XY: 0.238 AC XY: 17708 AN XY: 74256

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: 88 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12307 AN: 67948

Other (OTH) AF: 0.249 AC: 525 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.72
DANN	Benign	0.17
PhyloP100		-2.1
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: rs34571439; hg19: chr10-95351310;