Variant 19-16890349-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003950.4(F2RL3):c.886T>C(p.Phe296Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000562 in 1,601,660 control chromosomes in the GnomAD database, including 1 homozygotes. 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. F296V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00058 ( 1 hom. )

Consequence

F2RL3
NM_003950.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.83

Variant links:

Genes affected

F2RL3 (HGNC:3540): (F2R like thrombin or trypsin receptor 3) This gene encodes a member of the protease-activated receptor subfamily, part of the G-protein coupled receptor 1 family of proteins. The encoded receptor is proteolytically processed to reveal an extracellular N-terminal tethered ligand that binds to and activates the receptor. This receptor plays a role in blood coagulation, inflammation and response to pain. Hypomethylation at this gene may be associated with lung cancer in human patients. [provided by RefSeq, Sep 2016]

F2RL3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.086422056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F2RL3	NM_003950.4 linkuse as main transcript	c.886T>C	p.Phe296Leu	missense_variant	2/2	ENST00000248076.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F2RL3	ENST00000248076.4 linkuse as main transcript	c.886T>C	p.Phe296Leu	missense_variant	2/2	1	NM_003950.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000322

AC:

AN:

226598

Hom.:

AF XY:

0.000352

AC XY:

AN XY:

124834

show subpopulations

Gnomad AFR exome

AF:

0.000217

Gnomad AMR exome

AF:

0.000515

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000116

Gnomad SAS exome

AF:

0.0000681

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000463

Gnomad OTH exome

AF:

0.000354

GnomAD4 exome

AF:

0.000584

AC:

846

AN:

1449304

Hom.:

Cov.:

AF XY:

0.000585

AC XY:

422

AN XY:

720916

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.000389

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000586

Gnomad4 FIN exome

AF:

0.0000213

Gnomad4 NFE exome

AF:

0.000726

Gnomad4 OTH exome

AF:

0.000233

GnomAD4 genome

AF:

0.000354

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000264

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000335

Hom.:

Bravo

AF:

0.000359

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000298

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

Eigen

Benign

-0.063

Eigen_PC

Benign

0.046

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.70

M_CAP

Benign

0.057

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

0.95

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.20

Sift

Benign

0.094

Sift4G

Benign

0.27

Polyphen

0.12

Vest4

0.23

MutPred

0.55

Loss of helix (P = 0.0444);

MVP

0.77

MPC

0.34

ClinPred

0.42

GERP RS

4.2

Varity_R

0.37

gMVP

0.52

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over