Genetic Variant FFAR2:p.Leu211His (chr19-35450346-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.38

Publications

18 publications found

Variant links:

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]

FFAR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FFAR2	NM_001370087.1 link	c.632T>A	p.Leu211His	missense_variant	Exon 2 of 2	ENST00000599180.3	NP_001357016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FFAR2	ENST00000599180.3 link	c.632T>A	p.Leu211His	missense_variant	Exon 2 of 2	1	NM_001370087.1	ENSP00000473159.1	O15552
FFAR2	ENST00000246549.2 link	c.632T>A	p.Leu211His	missense_variant	Exon 1 of 1	6		ENSP00000246549.2	O15552
FFAR2	ENST00000601590.1 link	n.17-807T>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0547

AC:

8316

AN:

152118

Hom.:

296

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0752

AC XY:

54673

AN XY:

727244

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

6669

13337

20006

26674

33343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3102

6204

9306

12408

15510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0546

AC:

8316

AN:

152236

Hom.:

296

Cov.:

AF XY:

0.0544

AC XY:

4052

AN XY:

74452

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0727

AC:

4944

AN:

68008

Other (OTH)

AF:

0.0555

AC:

117

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

402

804

1205

1607

2009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.089

.;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.2

N;N

PhyloP100

4.4

PrimateAI

Benign

0.45

PROVEAN

Benign

4.9

.;N

REVEL

Benign

0.12

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.044

MPC

0.24

ClinPred

0.0048

GERP RS

5.5

Varity_R

0.096

gMVP

0.54

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over