chr19-35352183-G-A

Variant names:

• chr19-35352183-G-A
• rs2301151
• NM_005303.3:c.632G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 0.83 (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
• Publications: 44 publications found

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]

ENSG00000288731 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005303.3. 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
	FFAR1	NM_005303.3	MANE Select	c.632G>A	p.Arg211His	missense	Exon 2 of 2	NP_005294.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR1	ENST00000246553.4	TSL:6 MANE Select	c.632G>A	p.Arg211His	missense	Exon 2 of 2	ENSP00000246553.2
	FFAR1	ENST00000950226.1		c.632G>A	p.Arg211His	missense	Exon 2 of 2	ENSP00000620285.1
	ENSG00000288731	ENST00000716259.1		n.771-4561C>T		intron	N/A

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

GnomAD2 exomes AF: 0.812 AC: 189717 AN: 233752 AF XY: 0.814

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 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

African (AFR) AF: 0.963 AC: 32126 AN: 33344

American (AMR) AF: 0.810 AC: 35677 AN: 44070

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 22259 AN: 26004

East Asian (EAS) AF: 0.794 AC: 31319 AN: 39424

South Asian (SAS) AF: 0.903 AC: 77280 AN: 85580

European-Finnish (FIN) AF: 0.736 AC: 35588 AN: 48360

Middle Eastern (MID) AF: 0.935 AC: 5382 AN: 5758

European-Non Finnish (NFE) AF: 0.750 AC: 832683 AN: 1109646

Other (OTH) AF: 0.807 AC: 48457 AN: 60064

GnomAD4 genome AF: 0.834 AC: 126936 AN: 152186 Hom.: 53523 Cov.: 33 AF XY: 0.833 AC XY: 61962 AN XY: 74390

African (AFR) AF: 0.953 AC: 39597 AN: 41560

American (AMR) AF: 0.828 AC: 12674 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2979 AN: 3472

East Asian (EAS) AF: 0.804 AC: 4125 AN: 5130

South Asian (SAS) AF: 0.912 AC: 4401 AN: 4824

European-Finnish (FIN) AF: 0.739 AC: 7844 AN: 10610

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52375 AN: 67968

Other (OTH) AF: 0.862 AC: 1822 AN: 2114

Alfa AF: 0.792 Hom.: 123952

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 v4.9

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
PhyloP100		0.27
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
Mutation Taster		=91/9	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: rs2301151; hg19: chr19-35843086; COSMIC: COSV50051321; COSMIC: COSV50051321;