10-93587284-G-C

Position:

• chr10-93587284-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000371481.9(FFAR4):​c.761G>C​(p.Arg254Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R254H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FFAR4 ENST00000371481.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

Genes affected

FFAR4 (HGNC:19061): (free fatty acid receptor 4) This gene encodes a G protein-coupled receptor (GPR) which belongs to the rhodopsin family of GPRs. The encoded protein functions as a receptor for free fatty acids, including omega-3, and participates in suppressing anti-inflammatory responses and insulin sensitizing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FFAR4	NM_001195755.2	c.761G>C	p.Arg254Pro	missense_variant	3/3	ENST00000371481.9	NP_001182684.1
FFAR4	NM_181745.4	c.809G>C	p.Arg270Pro	missense_variant	4/4		NP_859529.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FFAR4	ENST00000371481.9	c.761G>C	p.Arg254Pro	missense_variant	3/3	1	NM_001195755.2	ENSP00000360536	P1
FFAR4	ENST00000371483.8	c.809G>C	p.Arg270Pro	missense_variant	4/4	1		ENSP00000360538
FFAR4	ENST00000604414.1	c.696+11065G>C		intron_variant		3		ENSP00000474477

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.5	.;M
MutationTaster	Benign	0.69	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.2	D;N
REVEL	Uncertain	0.47
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.085	T;T
Polyphen		0.96	D;D
Vest4		0.25
MutPred		0.75		.;Loss of MoRF binding (P = 0.0464);
MVP		0.90
MPC		1.7
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.91
gMVP		0.92

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: rs116454156; hg19: chr10-95347041;