19-16889921-C-T

Variant names:

• chr19-16889921-C-T
• rs558028827
• NM_003950.4:c.458C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003950.4(F2RL3):​c.458C>T​(p.Thr153Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000871 in 1,583,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000082 (1 hom.)
• Consequence: F2RL3 NM_003950.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050180197).

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.458C>T	p.Thr153Met	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.458C>T	p.Thr153Met	missense	Exon 2 of 2	ENSP00000248076.2	Q96RI0
	F2RL3	ENST00000599210.1	TSL:2	c.*112C>T		3_prime_UTR	Exon 2 of 2	ENSP00000471518.1	M0R0Y0

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000142 AC: 27 AN: 190656 AF XY: 0.000142

Gnomad AFR exome AF: 0.0000898

Gnomad AMR exome AF: 0.000100

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000720

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000824 AC: 118 AN: 1431686 Hom.: 1 Cov.: 33 AF XY: 0.0000858 AC XY: 61 AN XY: 711116

African (AFR) AF: 0.0000603 AC: 2 AN: 33166

American (AMR) AF: 0.000121 AC: 5 AN: 41390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25610

East Asian (EAS) AF: 0.000412 AC: 16 AN: 38804

South Asian (SAS) AF: 0.0000594 AC: 5 AN: 84218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.0000717 AC: 79 AN: 1101596

Other (OTH) AF: 0.000185 AC: 11 AN: 59382

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152278 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74450

African (AFR) AF: 0.0000481 AC: 2 AN: 41562

American (AMR) AF: 0.000131 AC: 2 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68002

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.000129 Hom.: 0

Bravo AF: 0.0000718

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000162 AC: 19

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.084
Sift	Benign	0.11	T
Sift4G	Benign	0.20	T
Polyphen		0.64	P
Vest4		0.16
MVP		0.47
MPC		0.22
ClinPred		0.024	T
GERP RS		0.95
Varity_R		0.032
gMVP		0.39
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs558028827; hg19: chr19-17000732; COSMIC: COSV50185478; COSMIC: COSV50185478;