chr19-35352183-G-C

Position:

• chr19-35352183-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005303.3(FFAR1):​c.632G>C​(p.Arg211Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R211H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29372662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FFAR1	NM_005303.3	c.632G>C	p.Arg211Pro	missense_variant	2/2	ENST00000246553.4	NP_005294.1
FFAR1	XM_047438698.1	c.632G>C	p.Arg211Pro	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>C	p.Arg211Pro	missense_variant	2/2	6	NM_005303.3	ENSP00000246553.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 90

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.8
DANN	Benign	0.94
DEOGEN2	Uncertain	0.67	D
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.17
Sift	Benign	0.080	T
Sift4G	Benign	0.081	T
Polyphen		0.92	P
Vest4		0.22
MutPred		0.53		Loss of MoRF binding (P = 6e-04);
MVP		0.52
MPC		1.5
ClinPred		0.90	D
GERP RS		-4.6
Varity_R		0.66
gMVP		0.80

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;