Variant 10-93587279-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001195755.2(FFAR4):c.756G>C(p.Gln252His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,614,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

FFAR4
NM_001195755.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04282692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FFAR4	NM_001195755.2 linkuse as main transcript	c.756G>C	p.Gln252His	missense_variant	3/3	ENST00000371481.9
FFAR4	NM_181745.4 linkuse as main transcript	c.804G>C	p.Gln268His	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FFAR4	ENST00000371481.9 linkuse as main transcript	c.756G>C	p.Gln252His	missense_variant	3/3	1	NM_001195755.2	P1	Q5NUL3-2
FFAR4	ENST00000371483.8 linkuse as main transcript	c.804G>C	p.Gln268His	missense_variant	4/4	1			Q5NUL3-1
FFAR4	ENST00000604414.1 linkuse as main transcript	c.696+11060G>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000151

AC:

AN:

251406

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.000325

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000426

AC:

623

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000378

AC XY:

275

AN XY:

727240

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000513

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.000236

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000572

Hom.:

Bravo

AF:

0.000230

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000415

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 submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.804G>C (p.Q268H) alteration is located in exon 4 (coding exon 4) of the FFAR4 gene. This alteration results from a G to C substitution at nucleotide position 804, causing the glutamine (Q) at amino acid position 268 to be replaced by a histidine (H). 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

0.16

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.87

MutationTaster

Benign

0.50

D;D

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.039

Sift

Benign

0.25

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0010

B;B

Vest4

0.076

MutPred

0.51

.;Gain of disorder (P = 0.095);

MVP

0.81

MPC

0.51

ClinPred

0.048

GERP RS

3.0

Varity_R

0.11

gMVP

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over