rs2227356

Positions:

• chr19-16892594-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003950.4(F2RL3):​c.*1973C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 167,640 control chromosomes in the GnomAD database, including 6,458 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 0.26 (5967 hom., cov: 31)
  • Exomes 𝑓: 0.22 (491 hom.)
• Consequence: F2RL3 NM_003950.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F2RL3	NM_003950.4	c.*1973C>T		3_prime_UTR_variant	2/2	ENST00000248076.4	NP_003941.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2RL3	ENST00000248076.4	c.*1973C>T		3_prime_UTR_variant	2/2	1	NM_003950.4	ENSP00000248076.2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38963 AN: 151808 Hom.: 5966 Cov.: 31

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0629

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.222 AC: 3495 AN: 15712 Hom.: 491 Cov.: 0 AF XY: 0.225 AC XY: 1879 AN XY: 8362

Gnomad4 AFR exome AF: 0.0641

Gnomad4 AMR exome AF: 0.237

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.0405

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.257 AC: 38986 AN: 151928 Hom.: 5967 Cov.: 31 AF XY: 0.257 AC XY: 19067 AN XY: 74240

Gnomad4 AFR AF: 0.0992

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.0633

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.284

Alfa AF: 0.323 Hom.: 13093

Bravo AF: 0.246

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs2227356; hg19: chr19-17003405;