chr19-51746043-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002029.4(FPR1):​c.952G>A​(p.Ala318Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

FPR1
NM_002029.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.585
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03476581).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FPR1NM_002029.4 linkuse as main transcriptc.952G>A p.Ala318Thr missense_variant 2/2 ENST00000304748.5 NP_002020.1 P21462
FPR1NM_001193306.2 linkuse as main transcriptc.952G>A p.Ala318Thr missense_variant 3/3 NP_001180235.1 P21462

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FPR1ENST00000304748.5 linkuse as main transcriptc.952G>A p.Ala318Thr missense_variant 2/21 NM_002029.4 ENSP00000302707.3 P21462
FPR1ENST00000594900.2 linkuse as main transcriptc.952G>A p.Ala318Thr missense_variant 3/34 ENSP00000470750.2 P21462M0QZT0
FPR1ENST00000595042.5 linkuse as main transcriptc.952G>A p.Ala318Thr missense_variant 3/32 ENSP00000471493.1 P21462
FPR1ENST00000600815.2 linkuse as main transcriptc.952G>A p.Ala318Thr missense_variant 2/23 ENSP00000472936.2 P21462M0R315

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000717
AC:
18
AN:
250976
Hom.:
0
AF XY:
0.0000737
AC XY:
10
AN XY:
135632
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000237
AC:
347
AN:
1461886
Hom.:
0
Cov.:
72
AF XY:
0.000231
AC XY:
168
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000298
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000889
Hom.:
0
Bravo
AF:
0.0000378
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000741
AC:
9
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 318 of the FPR1 protein (p.Ala318Thr). This variant is present in population databases (rs201404212, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FPR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 840695). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
4.8
DANN
Benign
0.80
DEOGEN2
Benign
0.068
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.025
N
LIST_S2
Benign
0.15
.;T
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.035
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.1
.;N
REVEL
Benign
0.035
Sift
Benign
0.60
.;T
Sift4G
Benign
0.39
T;T
Polyphen
0.013
B;B
Vest4
0.034
MVP
0.34
MPC
0.30
ClinPred
0.018
T
GERP RS
1.3
Varity_R
0.034
gMVP
0.056

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.

Other links and lift over

dbSNP: rs201404212; hg19: chr19-52249296; COSMIC: COSV59051442; COSMIC: COSV59051442; API