19-51746963-A-C

Variant names:

• chr19-51746963-A-C
• rs5030878
• NM_002029.4:c.32T>G

Variant summary

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

The NM_002029.4(FPR1):​c.32T>G​(p.Ile11Ser) 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. 15/24 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. I11T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.885
• Publications: 47 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	NM_002029.4	MANE Select	c.32T>G	p.Ile11Ser	missense	Exon 2 of 2	NP_002020.1
	FPR1	NM_001193306.2		c.32T>G	p.Ile11Ser	missense	Exon 3 of 3	NP_001180235.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	ENST00000304748.5	TSL:1 MANE Select	c.32T>G	p.Ile11Ser	missense	Exon 2 of 2	ENSP00000302707.3
	FPR1	ENST00000594900.2	TSL:4	c.32T>G	p.Ile11Ser	missense	Exon 3 of 3	ENSP00000470750.2
	FPR1	ENST00000595042.5	TSL:2	c.32T>G	p.Ile11Ser	missense	Exon 3 of 3	ENSP00000471493.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.052
DANN	Benign	0.65
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.89
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.69	N
REVEL	Benign	0.035
Sift	Benign	0.77	T
Sift4G	Benign	0.89	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.36		Gain of disorder (P = 0.0052)
MVP		0.099
MPC		0.44
ClinPred		0.073	T
GERP RS		-6.9
Varity_R		0.045
gMVP		0.20
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5030878; hg19: chr19-52250216;