NM_001370087.1:c.425C>T

Variant names:

• chr19-35450139-C-T
• NM_001370087.1:c.425C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370087.1(FFAR2):​c.425C>T​(p.Thr142Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FFAR2 NM_001370087.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.517
• Publications: 0 publications found

Genes affected

FFAR2 (HGNC:4501): (free fatty acid receptor 2) 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 short chain free fatty acids and may be involved in the inflammatory response and in regulating lipid plasma levels. [provided by RefSeq, Apr 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31975067).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370087.1. 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
	FFAR2	NM_001370087.1	MANE Select	c.425C>T	p.Thr142Ile	missense	Exon 2 of 2	NP_001357016.1	C6KYL4
	FFAR2	NM_005306.3		c.425C>T	p.Thr142Ile	missense	Exon 3 of 3	NP_005297.1	C6KYL4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR2	ENST00000599180.3	TSL:1 MANE Select	c.425C>T	p.Thr142Ile	missense	Exon 2 of 2	ENSP00000473159.1	O15552
	FFAR2	ENST00000246549.2	TSL:6	c.425C>T	p.Thr142Ile	missense	Exon 1 of 1	ENSP00000246549.2	O15552
	FFAR2	ENST00000601590.1	TSL:5	n.17-1014C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.52
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.35
Sift	Benign	0.034	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.94	P
Vest4		0.10
MutPred		0.54		Loss of catalytic residue at T142 (P = 0.0601)
MVP		0.77
MPC		0.66
ClinPred		0.77	D
GERP RS		0.77
PromoterAI		0.0032	Neutral
Varity_R		0.17
gMVP		0.46
Mutation Taster		=81/19	polymorphism

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

hg19: chr19-35941041;