rs409093

chr19-35450346-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370087.1(FFAR2):c.632T>A(p.Leu211His) variant causes a missense change. The variant allele was found at a frequency of 0.0717 in 1,614,116 control chromosomes in the GnomAD database, including 4,781 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.055 (296 hom., cov: 32)
  • Exomes 𝑓: 0.074 (4485 hom.)
• Consequence: FFAR2 NM_001370087.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38

Genes affected

FFAR2 (HGNC:4501): (free fatty acid receptor 2) This gene encodes a member of the GP40 family of G protein-coupled receptors that are clustered together on chromosome 19. The encoded protein is a receptor for short chain free fatty acids and may be involved in the inflammatory response and in regulating lipid plasma levels. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001258254).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FFAR2	NM_001370087.1	c.632T>A	p.Leu211His	missense_variant	2/2	ENST00000599180.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FFAR2	ENST00000599180.3	c.632T>A	p.Leu211His	missense_variant	2/2	1	NM_001370087.1	P1
FFAR2	ENST00000246549.2	c.632T>A	p.Leu211His	missense_variant	1/1			P1
FFAR2	ENST00000601590.1	n.17-807T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8316 AN: 152118 Hom.: 296 Cov.: 32

Gnomad AFR AF: 0.0288

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0727

Gnomad OTH AF: 0.0560

GnomAD3 exomes AF: 0.0636 AC: 15982 AN: 251360 Hom.: 715 AF XY: 0.0684 AC XY: 9300 AN XY: 135886

Gnomad AFR exome AF: 0.0278

Gnomad AMR exome AF: 0.0231

Gnomad ASJ exome AF: 0.0805

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.122

Gnomad FIN exome AF: 0.0670

Gnomad NFE exome AF: 0.0735

Gnomad OTH exome AF: 0.0600

GnomAD4 exome AF: 0.0735 AC: 107450 AN: 1461880 Hom.: 4485 Cov.: 33 AF XY: 0.0752 AC XY: 54673 AN XY: 727244

Gnomad4 AFR exome AF: 0.0283

Gnomad4 AMR exome AF: 0.0239

Gnomad4 ASJ exome AF: 0.0823

Gnomad4 EAS exome AF: 0.000831

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0723

Gnomad4 NFE exome AF: 0.0761

Gnomad4 OTH exome AF: 0.0671

GnomAD4 genome AF: 0.0546 AC: 8316 AN: 152236 Hom.: 296 Cov.: 32 AF XY: 0.0544 AC XY: 4052 AN XY: 74452

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.0302

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0662

Gnomad4 NFE AF: 0.0727

Gnomad4 OTH AF: 0.0555

Alfa AF: 0.0692 Hom.: 276

Bravo AF: 0.0495

TwinsUK AF: 0.0747 AC: 277

ALSPAC AF: 0.0833 AC: 321

ESP6500AA AF: 0.0322 AC: 142

ESP6500EA AF: 0.0724 AC: 623

ExAC AF: 0.0656 AC: 7969

Asia WGS AF: 0.0540 AC: 188 AN: 3478

EpiCase AF: 0.0713

EpiControl AF: 0.0708

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	15
Dann	Benign	0.21
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.15	N
MetaRNN	Benign	0.0013	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.2	N;N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.45	T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.044
MPC		0.24
ClinPred		0.0048	T
GERP RS		5.5
Varity_R		0.096
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs409093; hg19: chr19-35941248;