rs1555796364

Positions:

• chr19-51746168-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30399245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPR1	NM_002029.4	c.827A>G	p.Tyr276Cys	missense_variant	2/2	ENST00000304748.5	NP_002020.1
FPR1	NM_001193306.2	c.827A>G	p.Tyr276Cys	missense_variant	3/3		NP_001180235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPR1	ENST00000304748.5	c.827A>G	p.Tyr276Cys	missense_variant	2/2	1	NM_002029.4	ENSP00000302707	P1
FPR1	ENST00000594900.2	c.827A>G	p.Tyr276Cys	missense_variant	3/3	4		ENSP00000470750	P1
FPR1	ENST00000595042.5	c.827A>G	p.Tyr276Cys	missense_variant	3/3	2		ENSP00000471493	P1
FPR1	ENST00000600815.2	c.827A>G	p.Tyr276Cys	missense_variant	2/2	3		ENSP00000472936	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Gingival disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 03, 2017

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FPR1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 276 of the FPR1 protein (p.Tyr276Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. -

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.2	.;D
REVEL	Benign	0.15
Sift	Benign	0.15	.;T
Sift4G	Benign	0.19	T;T
Polyphen		0.83	P;P
Vest4		0.20
MutPred		0.60		Gain of methylation at K277 (P = 0.0136);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

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: rs1555796364; hg19: chr19-52249421;