Genetic Variant F2RL3:p.Phe296Leu (chr19-16890349-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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.

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

Publications

13 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003950.4. 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
	F2RL3	NM_003950.4	MANE Select	c.886T>C	p.Phe296Leu	missense	Exon 2 of 2	NP_003941.2	Q96RI0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F2RL3	ENST00000248076.4	TSL:1 MANE Select	c.886T>C	p.Phe296Leu	missense	Exon 2 of 2	ENSP00000248076.2	Q96RI0

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

GnomAD2 exomes

AF:

0.000322

AC:

AN:

226598

AF XY:

0.000352

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 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

African (AFR)

AF:

0.0000601

AC:

AN:

33298

American (AMR)

AF:

0.000389

AC:

AN:

43694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25926

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39316

South Asian (SAS)

AF:

0.0000586

AC:

AN:

85268

European-Finnish (FIN)

AF:

0.0000213

AC:

AN:

46880

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000726

AC:

805

AN:

1109174

Other (OTH)

AF:

0.000233

AC:

AN:

59990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000354

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000264

AC:

AN:

41598

American (AMR)

AF:

0.000131

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000327

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

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

PhyloP100

3.8

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

Mutation Taster

=86/14

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over