Variant chr19-35352183-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005303.3(FFAR1):c.632G>A(p.Arg211His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 1,604,436 control chromosomes in the GnomAD database, including 488,197 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.83 ( 53523 hom., cov: 33)

Exomes 𝑓: 0.77 ( 434674 hom. )

Consequence

FFAR1
NM_005303.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.274

Variant links:

Genes affected

FFAR1 (HGNC:4498): (free fatty acid receptor 1) 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 medium and long chain free fatty acids and may be involved in the metabolic regulation of insulin secretion. Polymorphisms in this gene may be associated with type 2 diabetes. [provided by RefSeq, Apr 2009]

FFAR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.4595264E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FFAR1	NM_005303.3 linkuse as main transcript	c.632G>A	p.Arg211His	missense_variant	2/2	ENST00000246553.4	NP_005294.1	O14842
FFAR1	XM_047438698.1 linkuse as main transcript	c.632G>A	p.Arg211His	missense_variant	2/2		XP_047294654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FFAR1	ENST00000246553.4 linkuse as main transcript	c.632G>A	p.Arg211His	missense_variant	2/2	6	NM_005303.3	ENSP00000246553.2		O14842

Frequencies

GnomAD3 genomes

AF:

0.834

AC:

126813

AN:

152068

Hom.:

53461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.953

Gnomad AMI

AF:

0.925

Gnomad AMR

AF:

0.828

Gnomad ASJ

AF:

0.858

Gnomad EAS

AF:

0.804

Gnomad SAS

AF:

0.912

Gnomad FIN

AF:

0.739

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.859

GnomAD3 exomes

AF:

0.812

AC:

189717

AN:

233752

Hom.:

77362

AF XY:

0.814

AC XY:

104086

AN XY:

127822

show subpopulations

Gnomad AFR exome

AF:

0.959

Gnomad AMR exome

AF:

0.804

Gnomad ASJ exome

AF:

0.860

Gnomad EAS exome

AF:

0.811

Gnomad SAS exome

AF:

0.903

Gnomad FIN exome

AF:

0.740

Gnomad NFE exome

AF:

0.775

Gnomad OTH exome

AF:

0.821

GnomAD4 exome

AF:

0.772

AC:

1120771

AN:

1452250

Hom.:

434674

Cov.:

AF XY:

0.776

AC XY:

560699

AN XY:

722422

show subpopulations

Gnomad4 AFR exome

AF:

0.963

Gnomad4 AMR exome

AF:

0.810

Gnomad4 ASJ exome

AF:

0.856

Gnomad4 EAS exome

AF:

0.794

Gnomad4 SAS exome

AF:

0.903

Gnomad4 FIN exome

AF:

0.736

Gnomad4 NFE exome

AF:

0.750

Gnomad4 OTH exome

AF:

0.807

GnomAD4 genome

AF:

0.834

AC:

126936

AN:

152186

Hom.:

53523

Cov.:

AF XY:

0.833

AC XY:

61962

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.953

Gnomad4 AMR

AF:

0.828

Gnomad4 ASJ

AF:

0.858

Gnomad4 EAS

AF:

0.804

Gnomad4 SAS

AF:

0.912

Gnomad4 FIN

AF:

0.739

Gnomad4 NFE

AF:

0.771

Gnomad4 OTH

AF:

0.862

Alfa

AF:

0.788

Hom.:

87187

Bravo

AF:

0.844

TwinsUK

AF:

0.745

AC:

2761

ALSPAC

AF:

0.748

AC:

2882

ESP6500AA

AF:

0.950

AC:

4166

ESP6500EA

AF:

0.779

AC:

6689

ExAC

AF:

0.809

AC:

97456

Asia WGS

AF:

0.866

AC:

3010

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.4

DANN

Benign

0.92

DEOGEN2

Benign

0.20

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.28

MetaRNN

Benign

6.5e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.23

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.7

REVEL

Benign

0.036

Sift

Benign

0.47

Sift4G

Benign

0.58

Polyphen

0.0010

Vest4

0.017

MPC

0.65

ClinPred

0.0036

GERP RS

-4.6

Varity_R

0.036

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over