rs5030880

chr19-51746427-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002029.4(FPR1):c.568A>T(p.Arg190Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,846 control chromosomes in the GnomAD database, including 14,182 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R190S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.12 (1176 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13006 hom.)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.104

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026525855).
• BP6: Variant 19-51746427-T-A is Benign according to our data. Variant chr19-51746427-T-A is described in ClinVar as [Benign]. Clinvar id is 834692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FPR1	NM_002029.4	c.568A>T	p.Arg190Trp	missense_variant	2/2	ENST00000304748.5
FPR1	NM_001193306.2	c.568A>T	p.Arg190Trp	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FPR1	ENST00000304748.5	c.568A>T	p.Arg190Trp	missense_variant	2/2	1	NM_002029.4	P1
FPR1	ENST00000594900.2	c.568A>T	p.Arg190Trp	missense_variant	3/3	4		P1
FPR1	ENST00000595042.5	c.568A>T	p.Arg190Trp	missense_variant	3/3	2		P1
FPR1	ENST00000600815.2	c.568A>T	p.Arg190Trp	missense_variant	2/2	3		P1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18393 AN: 151874 Hom.: 1173 Cov.: 31

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.0995

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.123

GnomAD3 exomes AF: 0.133 AC: 33346 AN: 251326 Hom.: 2505 AF XY: 0.136 AC XY: 18523 AN XY: 135818

Gnomad AFR exome AF: 0.0839

Gnomad AMR exome AF: 0.0851

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.196

Gnomad SAS exome AF: 0.186

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.130 AC: 189986 AN: 1461854 Hom.: 13006 Cov.: 72 AF XY: 0.131 AC XY: 95476 AN XY: 727230

Gnomad4 AFR exome AF: 0.0851

Gnomad4 AMR exome AF: 0.0876

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.121 AC: 18409 AN: 151992 Hom.: 1176 Cov.: 31 AF XY: 0.125 AC XY: 9285 AN XY: 74270

Gnomad4 AFR AF: 0.0881

Gnomad4 AMR AF: 0.0994

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.127

Alfa AF: 0.125 Hom.: 421

Bravo AF: 0.111

TwinsUK AF: 0.121 AC: 447

ALSPAC AF: 0.124 AC: 477

ESP6500AA AF: 0.0844 AC: 372

ESP6500EA AF: 0.128 AC: 1098

ExAC AF: 0.135 AC: 16337

Asia WGS AF: 0.176 AC: 609 AN: 3478

EpiCase AF: 0.123

EpiControl AF: 0.124

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1 Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 29, 2020	This variant is associated with the following publications: (PMID: 12595898) -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Gingival disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

N-FORMYLPEPTIDE RECEPTOR POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Apr 10, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	13
Dann	Uncertain	0.99
DEOGEN2	Benign	0.081	T;T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.15	N
MetaRNN	Benign	0.0027	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L;L;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
Sift4G	Uncertain	0.023	D;D;.
Polyphen		0.0020	B;B;.
Vest4		0.044
MPC		0.32
ClinPred		0.014	T
GERP RS		2.6
Varity_R		0.074
gMVP		0.63

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: rs5030880; hg19: chr19-52249680; COSMIC: COSV59051377; COSMIC: COSV59051377;