Variant 19-16889821-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
F2RL3	NM_003950.4 linkuse as main transcript	c.358G>A	p.Ala120Thr	missense_variant	2/2	ENST00000248076.4	NP_003941.2	Q96RI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2RL3	ENST00000248076.4 linkuse as main transcript	c.358G>A	p.Ala120Thr	missense_variant	2/2	1	NM_003950.4	ENSP00000248076.2		Q96RI0
F2RL3	ENST00000599210.1 linkuse as main transcript	c.*12G>A		3_prime_UTR_variant	2/2	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

GnomAD3 exomes

AF:

0.245

AC:

53808

AN:

219948

Hom.:

7519

AF XY:

0.241

AC XY:

29304

AN XY:

121784

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 SAS exome

AF:

0.271

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

Gnomad4 AFR exome

AF:

0.574

Gnomad4 AMR exome

AF:

0.257

Gnomad4 ASJ exome

AF:

0.261

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.189

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.308

AC:

46835

AN:

152060

Hom.:

9140

Cov.:

AF XY:

0.307

AC XY:

22840

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.559

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.253

Gnomad4 SAS

AF:

0.275

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.307

Alfa

AF:

0.212

Hom.:

5798

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2019	This variant is associated with the following publications: (PMID: 30347494, 30143503, 29748334, 25293779) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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

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

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