rs1555796364

Variant names:

• chr19-51746168-T-C
• rs1555796364
• NM_002029.4:c.827A>G

Variant summary

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

The NM_002029.4(FPR1):​c.827A>G​(p.Tyr276Cys) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y276H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.44
• Publications: 0 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=0.30399245).

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.827A>G	p.Tyr276Cys	missense	Exon 2 of 2	NP_002020.1
	FPR1	NM_001193306.2		c.827A>G	p.Tyr276Cys	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.827A>G	p.Tyr276Cys	missense	Exon 2 of 2	ENSP00000302707.3
	FPR1	ENST00000594900.2	TSL:4	c.827A>G	p.Tyr276Cys	missense	Exon 3 of 3	ENSP00000470750.2
	FPR1	ENST00000595042.5	TSL:2	c.827A>G	p.Tyr276Cys	missense	Exon 3 of 3	ENSP00000471493.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Gingival disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.1
DANN	Benign	0.66
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.4
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.15
Sift	Benign	0.15	T
Sift4G	Benign	0.19	T
Polyphen		0.83	P
Vest4		0.20
MutPred		0.60		Gain of methylation at K277 (P = 0.0136)
MVP		0.35
MPC		0.95
ClinPred		0.52	D
GERP RS		-7.3
Varity_R		0.073
gMVP		0.11
Mutation Taster		=99/1	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: rs1555796364; hg19: chr19-52249421;