NM_001370087.1:c.632T>A

Variant names:

• chr19-35450346-T-A
• rs409093
• NM_001370087.1:c.632T>A

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370087.1. 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
	FFAR2	NM_001370087.1	MANE Select	c.632T>A	p.Leu211His	missense	Exon 2 of 2	NP_001357016.1	C6KYL4
	FFAR2	NM_005306.3		c.632T>A	p.Leu211His	missense	Exon 3 of 3	NP_005297.1	C6KYL4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR2	ENST00000599180.3	TSL:1 MANE Select	c.632T>A	p.Leu211His	missense	Exon 2 of 2	ENSP00000473159.1	O15552
	FFAR2	ENST00000246549.2	TSL:6	c.632T>A	p.Leu211His	missense	Exon 1 of 1	ENSP00000246549.2	O15552
	FFAR2	ENST00000601590.1	TSL:5	n.17-807T>A		intron	N/A

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

GnomAD2 exomes AF: 0.0636 AC: 15982 AN: 251360 AF XY: 0.0684

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 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

African (AFR) AF: 0.0283 AC: 947 AN: 33480

American (AMR) AF: 0.0239 AC: 1069 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0823 AC: 2151 AN: 26136

East Asian (EAS) AF: 0.000831 AC: 33 AN: 39700

South Asian (SAS) AF: 0.119 AC: 10262 AN: 86258

European-Finnish (FIN) AF: 0.0723 AC: 3859 AN: 53410

Middle Eastern (MID) AF: 0.0787 AC: 454 AN: 5768

European-Non Finnish (NFE) AF: 0.0761 AC: 84623 AN: 1112008

Other (OTH) AF: 0.0671 AC: 4052 AN: 60396

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

African (AFR) AF: 0.0288 AC: 1197 AN: 41528

American (AMR) AF: 0.0302 AC: 462 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5174

South Asian (SAS) AF: 0.118 AC: 571 AN: 4828

European-Finnish (FIN) AF: 0.0662 AC: 703 AN: 10618

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0727 AC: 4944 AN: 68008

Other (OTH) AF: 0.0555 AC: 117 AN: 2110

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 v4.9

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
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.089	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.2	N
PhyloP100		4.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	4.9	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.044
MPC		0.24
ClinPred		0.0048	T
GERP RS		5.5
Varity_R		0.096
gMVP		0.54
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs409093; hg19: chr19-35941248;