10-93566946-T-G

Variant names:

Variant summary

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

The NM_001195755.2(FFAR4):c.226T>G(p.Cys76Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FFAR4
NM_001195755.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.868

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42389655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FFAR4	NM_001195755.2 link	c.226T>G	p.Cys76Gly	missense_variant	Exon 1 of 3	ENST00000371481.9	NP_001182684.1	Q5NUL3-2B4DWG6
FFAR4	NM_181745.4 link	c.226T>G	p.Cys76Gly	missense_variant	Exon 1 of 4		NP_859529.2	Q5NUL3-1B4DWG6
FFAR4	XM_011539746.4 link	c.226T>G	p.Cys76Gly	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.226T>G	p.Cys76Gly	missense_variant	Exon 1 of 3	1	NM_001195755.2	ENSP00000360536.5	Q5NUL3-2
FFAR4	ENST00000371483.8 link	c.226T>G	p.Cys76Gly	missense_variant	Exon 1 of 4	1		ENSP00000360538.4	Q5NUL3-1
FFAR4	ENST00000604414.1 link	c.226T>G	p.Cys76Gly	missense_variant	Exon 1 of 3	3		ENSP00000474477.1	S4R3L2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247256

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458570

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725742

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

44506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39598

South Asian (SAS)

AF:

0.00

AC:

AN:

85988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111476

Other (OTH)

AF:

0.00

AC:

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

The FFAR4 p.Cys76Gly variant was not identified in the literature nor was it identified in ClinVar, Cosmic or the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The variant was identified in dbSNP (ID: rs147767392). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Cys76 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.32

.;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.76

T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.6

M;M;.

PhyloP100

0.87

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.9

D;D;.

REVEL

Uncertain

0.35

Sift

Benign

0.15

T;T;.

Sift4G

Benign

0.20

T;T;T

Polyphen

0.33

B;P;.

Vest4

0.22

MVP

0.75

MPC

1.4

ClinPred

0.71

GERP RS

2.9

PromoterAI

0.021

Neutral

(source)

Varity_R

0.39

gMVP

0.37

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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10-93566946-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over