Variant chr19-35352204-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005303.3(FFAR1):c.653G>A(p.Arg218Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,440,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FFAR1
NM_005303.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

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 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=0.30438024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FFAR1	NM_005303.3 linkuse as main transcript	c.653G>A	p.Arg218Gln	missense_variant	2/2	ENST00000246553.4	NP_005294.1
FFAR1	XM_047438698.1 linkuse as main transcript	c.653G>A	p.Arg218Gln	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.653G>A	p.Arg218Gln	missense_variant	2/2		NM_005303.3	ENSP00000246553	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

209084

Hom.:

AF XY:

0.0000262

AC XY:

AN XY:

114512

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000322

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000144

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1440254

Hom.:

Cov.:

AF XY:

0.0000182

AC XY:

AN XY:

715688

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000178

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000418

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.653G>A (p.R218Q) alteration is located in exon 1 (coding exon 1) of the FFAR1 gene. This alteration results from a G to A substitution at nucleotide position 653, causing the arginine (R) at amino acid position 218 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.81

M_CAP

Benign

0.036

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.75

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.9

REVEL

Benign

0.26

Sift

Benign

0.077

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.17

MutPred

0.48

Loss of MoRF binding (P = 0.0413);

MVP

0.92

MPC

1.5

ClinPred

0.77

GERP RS

4.0

Varity_R

0.18

gMVP

0.50

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over