19-51746507-C-A

Variant names:

• chr19-51746507-C-A
• rs111768566
• NM_002029.4:c.488G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002029.4(FPR1):​c.488G>T​(p.Arg163Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R163H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92
• Publications: 8 publications found

Genes affected

FPR1 (HGNC:3826): (formyl peptide receptor 1) This gene encodes a G protein-coupled receptor of mammalian phagocytic cells that is a member of the G-protein coupled receptor 1 family. The protein mediates the response of phagocytic cells to invasion of the host by microorganisms and is important in host defense and inflammation.[provided by RefSeq, Jul 2010]

FPR1 Gene-Disease associations (from GenCC):

• susceptibility to localized juvenile periodontitis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25849715).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002029.4. 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
	FPR1	NM_002029.4	MANE Select	c.488G>T	p.Arg163Leu	missense	Exon 2 of 2	NP_002020.1	P21462
	FPR1	NM_001193306.2		c.488G>T	p.Arg163Leu	missense	Exon 3 of 3	NP_001180235.1	P21462

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	ENST00000304748.5	TSL:1 MANE Select	c.488G>T	p.Arg163Leu	missense	Exon 2 of 2	ENSP00000302707.3	P21462
	FPR1	ENST00000594900.2	TSL:4	c.488G>T	p.Arg163Leu	missense	Exon 3 of 3	ENSP00000470750.2	P21462
	FPR1	ENST00000595042.5	TSL:2	c.488G>T	p.Arg163Leu	missense	Exon 3 of 3	ENSP00000471493.1	P21462

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 76

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	5.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.53	N
PhyloP100		2.9
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.17
Sift	Benign	0.057	T
Sift4G	Benign	0.17	T
Polyphen		0.010	B
Vest4		0.28
MutPred		0.66		Gain of glycosylation at T166 (P = 0.0555)
MVP		0.76
MPC		0.38
ClinPred		0.25	T
GERP RS		2.6
Varity_R		0.076
gMVP		0.58
Mutation Taster		=97/3	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: rs111768566; hg19: chr19-52249760;