Genetic Variant NM_001195755.2:c.434G>T (chr10-93567154-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001195755.2(FFAR4):c.434G>T(p.Arg145Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. R145H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FFAR4
NM_001195755.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.524

Publications

0 publications found

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]

FFAR4 links:

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ACMG classification

Classification was made for transcript

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=0.23554462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FFAR4	NM_001195755.2 link	c.434G>T	p.Arg145Leu	missense_variant	Exon 1 of 3	ENST00000371481.9	NP_001182684.1	Q5NUL3-2B4DWG6
FFAR4	NM_181745.4 link	c.434G>T	p.Arg145Leu	missense_variant	Exon 1 of 4		NP_859529.2	Q5NUL3-1B4DWG6
FFAR4	XM_011539746.4 link	c.434G>T	p.Arg145Leu	missense_variant	Exon 1 of 3		XP_011538048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FFAR4	ENST00000371481.9 link	c.434G>T	p.Arg145Leu	missense_variant	Exon 1 of 3	1	NM_001195755.2	ENSP00000360536.5	Q5NUL3-2
FFAR4	ENST00000371483.8 link	c.434G>T	p.Arg145Leu	missense_variant	Exon 1 of 4	1		ENSP00000360538.4	Q5NUL3-1
FFAR4	ENST00000604414.1 link	c.434G>T	p.Arg145Leu	missense_variant	Exon 1 of 3	3		ENSP00000474477.1	S4R3L2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722866

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25972

East Asian (EAS)

AF:

0.00

AC:

AN:

39596

South Asian (SAS)

AF:

0.00

AC:

AN:

85908

European-Finnish (FIN)

AF:

0.0000211

AC:

AN:

47384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110458

Other (OTH)

AF:

0.00

AC:

AN:

60184

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.098

.;T;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

M;M;.

PhyloP100

0.52

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.7

N;N;.

REVEL

Benign

0.066

Sift

Benign

0.30

T;T;.

Sift4G

Benign

0.091

T;T;T

Polyphen

0.49

P;B;.

Vest4

0.42

MutPred

0.62

Loss of MoRF binding (P = 0.0148);Loss of MoRF binding (P = 0.0148);Loss of MoRF binding (P = 0.0148);

MVP

0.48

MPC

0.86

ClinPred

0.15

GERP RS

2.1

PromoterAI

0.025

Neutral

(source)

Varity_R

0.14

gMVP

0.50

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over