chr10-93566895-G-C

Variant names:

Variant summary

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

The NM_001195755.2(FFAR4):c.175G>C(p.Val59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,606,494 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FFAR4
NM_001195755.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

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=0.15197274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FFAR4	NM_001195755.2 link	c.175G>C	p.Val59Leu	missense_variant	Exon 1 of 3	ENST00000371481.9	NP_001182684.1	Q5NUL3-2B4DWG6
FFAR4	NM_181745.4 link	c.175G>C	p.Val59Leu	missense_variant	Exon 1 of 4		NP_859529.2	Q5NUL3-1B4DWG6
FFAR4	XM_011539746.4 link	c.175G>C	p.Val59Leu	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.175G>C	p.Val59Leu	missense_variant	Exon 1 of 3	1	NM_001195755.2	ENSP00000360536.5	Q5NUL3-2
FFAR4	ENST00000371483.8 link	c.175G>C	p.Val59Leu	missense_variant	Exon 1 of 4	1		ENSP00000360538.4	Q5NUL3-1
FFAR4	ENST00000604414.1 link	c.175G>C	p.Val59Leu	missense_variant	Exon 1 of 3	3		ENSP00000474477.1	S4R3L2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454330

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33292

American (AMR)

AF:

0.0000228

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:

0.00

AC:

AN:

50766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109776

Other (OTH)

AF:

0.0000166

AC:

AN:

60136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41430

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.175G>C (p.V59L) alteration is located in exon 1 (coding exon 1) of the FFAR4 gene. This alteration results from a G to C substitution at nucleotide position 175, causing the valine (V) at amino acid position 59 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

.;T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;.

PhyloP100

0.49

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.3

N;N;.

REVEL

Benign

0.12

Sift

Benign

0.069

T;T;.

Sift4G

Benign

0.25

T;T;T

Polyphen

0.088

B;B;.

Vest4

0.13

MutPred

0.52

Loss of catalytic residue at V59 (P = 0.0994);Loss of catalytic residue at V59 (P = 0.0994);Loss of catalytic residue at V59 (P = 0.0994);

MVP

0.53

MPC

0.56

ClinPred

0.34

GERP RS

5.2

PromoterAI

0.057

Neutral

(source)

Varity_R

0.17

gMVP

0.25

Mutation Taster

=97/3

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over