19-51746040-T-G

Position:

• chr19-51746040-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002029.4(FPR1):​c.955A>C​(p.Ser319Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15544382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPR1	NM_002029.4	c.955A>C	p.Ser319Arg	missense_variant	2/2	ENST00000304748.5	NP_002020.1
FPR1	NM_001193306.2	c.955A>C	p.Ser319Arg	missense_variant	3/3		NP_001180235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPR1	ENST00000304748.5	c.955A>C	p.Ser319Arg	missense_variant	2/2	1	NM_002029.4	ENSP00000302707.3
FPR1	ENST00000594900.2	c.955A>C	p.Ser319Arg	missense_variant	3/3	4		ENSP00000470750.2
FPR1	ENST00000595042.5	c.955A>C	p.Ser319Arg	missense_variant	3/3	2		ENSP00000471493.1
FPR1	ENST00000600815.2	c.955A>C	p.Ser319Arg	missense_variant	2/2	3		ENSP00000472936.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 72 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Sep 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	0.94	N
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.5	.;N
REVEL	Benign	0.050
Sift	Benign	0.12	.;T
Sift4G	Benign	0.49	T;T
Polyphen		0.026	B;B
Vest4		0.12
MutPred		0.39		Loss of glycosylation at S319 (P = 0.0313);Loss of glycosylation at S319 (P = 0.0313);
MVP		0.56
MPC		0.36
ClinPred		0.14	T
GERP RS		2.5
Varity_R		0.12
gMVP		0.089

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: rs1599806193; hg19: chr19-52249293;