Genetic Variant NM_001195755.2:c.175G>A (chr10-93566895-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001195755.2(FFAR4):c.175G>A(p.Val59Met) 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 1,454,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V59L) 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: 0.491

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27436876).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195755.2. 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
	FFAR4	NM_001195755.2	MANE Select	c.175G>A	p.Val59Met	missense	Exon 1 of 3	NP_001182684.1	Q5NUL3-2
	FFAR4	NM_181745.4		c.175G>A	p.Val59Met	missense	Exon 1 of 4	NP_859529.2	Q5NUL3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FFAR4	ENST00000371481.9	TSL:1 MANE Select	c.175G>A	p.Val59Met	missense	Exon 1 of 3	ENSP00000360536.5	Q5NUL3-2
FFAR4	ENST00000371483.8	TSL:1	c.175G>A	p.Val59Met	missense	Exon 1 of 4	ENSP00000360538.4	Q5NUL3-1
FFAR4	ENST00000944863.1		c.175G>A	p.Val59Met	missense	Exon 1 of 2	ENSP00000614922.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454326

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723338

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:

33292

American (AMR)

AF:

0.00

AC:

AN:

43948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26008

East Asian (EAS)

AF:

0.00

AC:

AN:

39254

South Asian (SAS)

AF:

0.00

AC:

AN:

85394

European-Finnish (FIN)

AF:

0.0000197

AC:

AN:

50764

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109774

Other (OTH)

AF:

0.00

AC:

AN:

60136

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), 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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

Eigen

Benign

-0.010

Eigen_PC

Benign

0.047

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.016

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

PhyloP100

0.49

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.5

REVEL

Benign

0.073

Sift

Uncertain

0.013

Sift4G

Uncertain

0.047

Polyphen

0.53

Vest4

0.28

MutPred

0.49

Loss of sheet (P = 0.1158)

MVP

0.69

MPC

1.3

ClinPred

0.93

GERP RS

5.2

PromoterAI

-0.043

Neutral

(source)

Varity_R

0.14

gMVP

0.23

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over