chr10-93566826-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 13/21 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

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.441
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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/exons MANE UniProt
FFAR4NM_001195755.2 linkuse as main transcriptc.106C>T p.Arg36Trp missense_variant 1/3 ENST00000371481.9
FFAR4NM_181745.4 linkuse as main transcriptc.106C>T p.Arg36Trp missense_variant 1/4
FFAR4XM_011539746.4 linkuse as main transcriptc.106C>T p.Arg36Trp missense_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FFAR4ENST00000371481.9 linkuse as main transcriptc.106C>T p.Arg36Trp missense_variant 1/31 NM_001195755.2 P1Q5NUL3-2
FFAR4ENST00000371483.8 linkuse as main transcriptc.106C>T p.Arg36Trp missense_variant 1/41 Q5NUL3-1
FFAR4ENST00000604414.1 linkuse as main transcriptc.106C>T p.Arg36Trp missense_variant 1/33

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152232
Hom.:
0
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.0000177
AC:
4
AN:
226350
Hom.:
0
AF XY:
0.0000243
AC XY:
3
AN XY:
123704
show subpopulations
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 SAS 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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000614
Gnomad4 OTH exome
AF:
0.0000834
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152232
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000727
Hom.:
0
Bravo
AF:
0.0000416

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 submitterclinical testingAmbry GeneticsJul 12, 2023The 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;.
MutationTaster
Benign
0.83
D;D
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
Varity_R
0.056
gMVP
0.70

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.

Other links and lift over

dbSNP: rs1270899968; hg19: chr10-95326583; API