19-16890349-T-G

Variant names:

• chr19-16890349-T-G
• rs2227346
• NM_003950.4:c.886T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003950.4(F2RL3):​c.886T>G​(p.Phe296Val) variant causes a missense change. The variant allele was found at a frequency of 0.00202 in 1,601,658 control chromosomes in the GnomAD database, including 59 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 0.011 (27 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (32 hom.)
• Consequence: F2RL3 NM_003950.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006087482).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0108 (1639/152354) while in subpopulation AFR AF = 0.037 (1539/41596). AF 95% confidence interval is 0.0355. There are 27 homozygotes in GnomAd4. There are 763 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

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>G	p.Phe296Val	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>G	p.Phe296Val	missense	Exon 2 of 2	ENSP00000248076.2	Q96RI0

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1636 AN: 152236 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00717

GnomAD2 exomes AF: 0.00263 AC: 596 AN: 226598 AF XY: 0.00203

Gnomad AFR exome AF: 0.0373

Gnomad AMR exome AF: 0.00215

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000295

Gnomad OTH exome AF: 0.000709

GnomAD4 exome AF: 0.00110 AC: 1591 AN: 1449304 Hom.: 32 Cov.: 33 AF XY: 0.000947 AC XY: 683 AN XY: 720916

African (AFR) AF: 0.0379 AC: 1262 AN: 33298

American (AMR) AF: 0.00211 AC: 92 AN: 43694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25926

East Asian (EAS) AF: 0.00 AC: 0 AN: 39316

South Asian (SAS) AF: 0.000117 AC: 10 AN: 85268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46880

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5758

European-Non Finnish (NFE) AF: 0.0000496 AC: 55 AN: 1109174

Other (OTH) AF: 0.00275 AC: 165 AN: 59990

GnomAD4 genome AF: 0.0108 AC: 1639 AN: 152354 Hom.: 27 Cov.: 33 AF XY: 0.0102 AC XY: 763 AN XY: 74508

African (AFR) AF: 0.0370 AC: 1539 AN: 41596

American (AMR) AF: 0.00496 AC: 76 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68022

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.0123

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0335 AC: 147

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00305 AC: 368

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-0.29	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		3.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.012	D
Polyphen		0.96	D
Vest4		0.38
MVP		0.88
MPC		0.59
ClinPred		0.046	T
GERP RS		4.2
Varity_R		0.58
gMVP		0.60
Mutation Taster		=92/8	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: rs2227346; hg19: chr19-17001160;