19-35352183-G-A

Position:

• chr19-35352183-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

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]

ACMG classification

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	c.632G>A	p.Arg211His	missense_variant	2/2	ENST00000246553.4	NP_005294.1
FFAR1	XM_047438698.1	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	c.632G>A	p.Arg211His	missense_variant	2/2	6	NM_005303.3	ENSP00000246553.2

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126813 AN: 152068 Hom.: 53461 Cov.: 33

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

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.: 90 AF XY: 0.776 AC XY: 560699 AN XY: 722422

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.: 33 AF XY: 0.833 AC XY: 61962 AN XY: 74390

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	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.4
DANN	Benign	0.92
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	6.5e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.036
Sift	Benign	0.47	T
Sift4G	Benign	0.58	T
Polyphen		0.0010	B
Vest4		0.017
MPC		0.65
ClinPred		0.0036	T
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

Other links and lift over

dbSNP: rs2301151; hg19: chr19-35843086; COSMIC: COSV50051321; COSMIC: COSV50051321;