NM_001195755.2:c.106C>T

Variant names:

• chr10-93566826-C-T
• rs1270899968
• NM_001195755.2:c.106C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195755.2(FFAR4):​c.106C>T​(p.Arg36Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000499 in 1,603,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: FFAR4 NM_001195755.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.441
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13839236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FFAR4	NM_001195755.2	c.106C>T	p.Arg36Trp	missense_variant	Exon 1 of 3	ENST00000371481.9	NP_001182684.1
FFAR4	NM_181745.4	c.106C>T	p.Arg36Trp	missense_variant	Exon 1 of 4		NP_859529.2
FFAR4	XM_011539746.4	c.106C>T	p.Arg36Trp	missense_variant	Exon 1 of 3		XP_011538048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FFAR4	ENST00000371481.9	c.106C>T	p.Arg36Trp	missense_variant	Exon 1 of 3	1	NM_001195755.2	ENSP00000360536.5
FFAR4	ENST00000371483.8	c.106C>T	p.Arg36Trp	missense_variant	Exon 1 of 4	1		ENSP00000360538.4
FFAR4	ENST00000604414.1	c.106C>T	p.Arg36Trp	missense_variant	Exon 1 of 3	3		ENSP00000474477.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000177 AC: 4 AN: 226350 AF XY: 0.0000243

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000295

Gnomad OTH exome AF: 0.000178

GnomAD4 exome AF: 0.0000510 AC: 74 AN: 1450864 Hom.: 0 Cov.: 32 AF XY: 0.0000541 AC XY: 39 AN XY: 721456

African (AFR) AF: 0.00 AC: 0 AN: 33202

American (AMR) AF: 0.00 AC: 0 AN: 44116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25928

East Asian (EAS) AF: 0.00 AC: 0 AN: 39180

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000614 AC: 68 AN: 1108376

Other (OTH) AF: 0.0000834 AC: 5 AN: 59924

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000727 Hom.: 0

Bravo AF: 0.0000416

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106C>T (p.R36W) alteration is located in exon 1 (coding exon 1) of the FFAR4 gene. This alteration results from a C to T substitution at nucleotide position 106, causing the arginine (R) at amino acid position 36 to be replaced by a tryptophan (W). 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	0.18
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	.;T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M;.
PhyloP100		0.44
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.13	N;N;.
REVEL	Benign	0.067
Sift	Benign	0.064	T;T;.
Sift4G	Uncertain	0.059	T;T;T
Polyphen		0.017	B;B;.
Vest4		0.17
MutPred		0.59		Loss of methylation at R36 (P = 0.0513);Loss of methylation at R36 (P = 0.0513);Loss of methylation at R36 (P = 0.0513);
MVP		0.38
MPC		0.55
ClinPred		0.20	T
GERP RS		2.2
PromoterAI		-0.0022	Neutral
Varity_R		0.056
gMVP		0.70
Mutation Taster		=84/16	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

dbSNP: rs1270899968; hg19: chr10-95326583;