chr19-51746069-C-T

Position:

chr19-51746069-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002029.4(FPR1):c.926G>A(p.Arg309Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,194 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 1 hom. )

Consequence

FPR1
NM_002029.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.1269573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPR1	NM_002029.4 linkuse as main transcript	c.926G>A	p.Arg309Gln	missense_variant	2/2	ENST00000304748.5	NP_002020.1	P21462
FPR1	NM_001193306.2 linkuse as main transcript	c.926G>A	p.Arg309Gln	missense_variant	3/3		NP_001180235.1	P21462

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FPR1	ENST00000304748.5 linkuse as main transcript	c.926G>A	p.Arg309Gln	missense_variant	2/2	1	NM_002029.4	ENSP00000302707.3	P21462
FPR1	ENST00000594900.2 linkuse as main transcript	c.926G>A	p.Arg309Gln	missense_variant	3/3	4		ENSP00000470750.2	P21462M0QZT0
FPR1	ENST00000595042.5 linkuse as main transcript	c.926G>A	p.Arg309Gln	missense_variant	3/3	2		ENSP00000471493.1	P21462
FPR1	ENST00000600815.2 linkuse as main transcript	c.926G>A	p.Arg309Gln	missense_variant	2/2	3		ENSP00000472936.2	P21462M0R315

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251178

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Gingival disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 27, 2023

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1036271). This variant has not been reported in the literature in individuals affected with FPR1-related conditions. This variant is present in population databases (rs555690623, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 309 of the FPR1 protein (p.Arg309Gln). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.79

.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.88

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.6

.;D

REVEL

Benign

0.18

Sift

Benign

0.18

.;T

Sift4G

Benign

0.14

T;T

Polyphen

0.79

P;P

Vest4

0.13

MVP

0.74

MPC

0.43

ClinPred

0.15

GERP RS

3.5

Varity_R

0.15

gMVP

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over