chr19-51746052-C-G

Variant names:

• chr19-51746052-C-G
• rs140083445
• NM_002029.4:c.943G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002029.4(FPR1):​c.943G>C​(p.Ala315Pro) 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. 13/22 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. A315T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55
• Publications: 2 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32004878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FPR1	NM_002029.4	c.943G>C	p.Ala315Pro	missense_variant	Exon 2 of 2	ENST00000304748.5	NP_002020.1
FPR1	NM_001193306.2	c.943G>C	p.Ala315Pro	missense_variant	Exon 3 of 3		NP_001180235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FPR1	ENST00000304748.5	c.943G>C	p.Ala315Pro	missense_variant	Exon 2 of 2	1	NM_002029.4	ENSP00000302707.3
FPR1	ENST00000594900.2	c.943G>C	p.Ala315Pro	missense_variant	Exon 3 of 3	4		ENSP00000470750.2
FPR1	ENST00000595042.5	c.943G>C	p.Ala315Pro	missense_variant	Exon 3 of 3	2		ENSP00000471493.1
FPR1	ENST00000600815.2	c.943G>C	p.Ala315Pro	missense_variant	Exon 2 of 2	3		ENSP00000472936.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.14	.;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L
PhyloP100		2.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.9	.;N
REVEL	Benign	0.057
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.024	B;B
Vest4		0.19
MutPred		0.77		Gain of catalytic residue at A315 (P = 0.0476);Gain of catalytic residue at A315 (P = 0.0476);
MVP		0.49
MPC		0.42
ClinPred		0.64	D
GERP RS		2.5
Varity_R		0.43
gMVP		0.40
Mutation Taster		=75/25	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: rs140083445; hg19: chr19-52249305; COSMIC: COSV59052249; COSMIC: COSV59052249;