dbSNP rs773902: F2RL3:p.Ala120Thr (chr19-16889821-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003950.4(F2RL3):c.358G>A(p.Ala120Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,597,532 control chromosomes in the GnomAD database, including 44,118 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 9140 hom., cov: 34)

Exomes 𝑓: 0.21 ( 34978 hom. )

Consequence

F2RL3
NM_003950.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.35

Publications

56 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.3480874E-5).

BP6

Variant 19-16889821-G-A is Benign according to our data. Variant chr19-16889821-G-A is described in ClinVar as Benign. ClinVar VariationId is 1182224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F2RL3	NM_003950.4 link	c.358G>A	p.Ala120Thr	missense_variant	Exon 2 of 2	ENST00000248076.4	NP_003941.2	Q96RI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F2RL3	ENST00000248076.4 link	c.358G>A	p.Ala120Thr	missense_variant	Exon 2 of 2	1	NM_003950.4	ENSP00000248076.2		Q96RI0
F2RL3	ENST00000599210.1 link	c.*12G>A		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000471518.1		M0R0Y0

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46758

AN:

151940

Hom.:

9114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.558

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.275

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.302

GnomAD2 exomes

AF:

0.245

AC:

53808

AN:

219948

AF XY:

0.241

show subpopulations

Gnomad AFR exome

AF:

0.574

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.210

AC:

302955

AN:

1445472

Hom.:

34978

Cov.:

AF XY:

0.212

AC XY:

152161

AN XY:

719312

show subpopulations

African (AFR)

AF:

0.574

AC:

19171

AN:

33426

American (AMR)

AF:

0.257

AC:

11310

AN:

44062

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

6777

AN:

26004

East Asian (EAS)

AF:

0.240

AC:

9470

AN:

39536

South Asian (SAS)

AF:

0.272

AC:

23380

AN:

85812

European-Finnish (FIN)

AF:

0.168

AC:

6834

AN:

40692

Middle Eastern (MID)

AF:

0.344

AC:

1975

AN:

5748

European-Non Finnish (NFE)

AF:

0.189

AC:

209989

AN:

1110152

Other (OTH)

AF:

0.234

AC:

14049

AN:

60040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

14939

29878

44816

59755

74694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7672

15344

23016

30688

38360

<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:

0.308

AC:

46835

AN:

152060

Hom.:

9140

Cov.:

AF XY:

0.307

AC XY:

22840

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.559

AC:

23168

AN:

41476

American (AMR)

AF:

0.279

AC:

4271

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

910

AN:

3464

East Asian (EAS)

AF:

0.253

AC:

1304

AN:

5156

South Asian (SAS)

AF:

0.275

AC:

1327

AN:

4824

European-Finnish (FIN)

AF:

0.176

AC:

1866

AN:

10608

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.193

AC:

13106

AN:

67926

Other (OTH)

AF:

0.307

AC:

648

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1504

3008

4513

6017

7521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.224

Hom.:

11349

Bravo

AF:

0.323

TwinsUK

AF:

0.193

AC:

717

ALSPAC

AF:

0.191

AC:

735

ESP6500AA

AF:

0.542

AC:

2354

ESP6500EA

AF:

0.200

AC:

1691

ExAC

AF:

0.237

AC:

28246

Asia WGS

AF:

0.294

AC:

1023

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30347494, 30143503, 29748334, 25293779) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.9

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.083

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.72

MetaRNN

Benign

0.000083

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

PhyloP100

1.3

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.66

REVEL

Benign

0.043

Sift

Benign

0.24

Sift4G

Benign

0.26

Polyphen

0.40

Vest4

0.056

MPC

0.15

ClinPred

0.0099

GERP RS

0.92

Varity_R

0.052

gMVP

0.18

Mutation Taster

=99/1

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over