rs1042229

chr19-51746419-A-Cchr19-51746419-A-G

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.576T>G(p.Asn192Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,613,830 control chromosomes in the GnomAD database, including 91,883 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. N192N) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.36 (10311 hom., cov: 31)
  • Exomes 𝑓: 0.33 (81572 hom.)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.296

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=0.0011065602).
• BP6: Variant 19-51746419-A-C is Benign according to our data. Variant chr19-51746419-A-C is described in ClinVar as [Benign]. Clinvar id is 402876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FPR1	NM_002029.4	c.576T>G	p.Asn192Lys	missense_variant	2/2	ENST00000304748.5
FPR1	NM_001193306.2	c.576T>G	p.Asn192Lys	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FPR1	ENST00000304748.5	c.576T>G	p.Asn192Lys	missense_variant	2/2	1	NM_002029.4	P1
FPR1	ENST00000594900.2	c.576T>G	p.Asn192Lys	missense_variant	3/3	4		P1
FPR1	ENST00000595042.5	c.576T>G	p.Asn192Lys	missense_variant	3/3	2		P1
FPR1	ENST00000600815.2	c.576T>G	p.Asn192Lys	missense_variant	2/2	3		P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54938 AN: 151860 Hom.: 10298 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.376

GnomAD3 exomes AF: 0.319 AC: 80159 AN: 251308 Hom.: 13345 AF XY: 0.321 AC XY: 43583 AN XY: 135826

Gnomad AFR exome AF: 0.464

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.279

Gnomad SAS exome AF: 0.317

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.331 AC: 484143 AN: 1461852 Hom.: 81572 Cov.: 70 AF XY: 0.331 AC XY: 241038 AN XY: 727238

Gnomad4 AFR exome AF: 0.472

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.362 AC: 54982 AN: 151978 Hom.: 10311 Cov.: 31 AF XY: 0.359 AC XY: 26692 AN XY: 74300

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.373

Alfa AF: 0.452 Hom.: 25591

TwinsUK AF: 0.337 AC: 1248

ALSPAC AF: 0.333 AC: 1282

ESP6500AA AF: 0.506 AC: 2231

ESP6500EA AF: 0.396 AC: 3403

ExAC AF: 0.327 AC: 39638

EpiCase AF: 0.350

EpiControl AF: 0.348

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Gingival disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 29, 2020

This variant is associated with the following publications: (PMID: 12595898) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.20
Dann	Benign	0.16
DEOGEN2	Benign	0.045	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0013	N
MetaRNN	Benign	0.0011	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.97	N;N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.016
MutPred		0.32		Gain of methylation at N192 (P = 0.0076);Gain of methylation at N192 (P = 0.0076);
MPC		0.35
ClinPred		0.00026	T
GERP RS		1.5
Varity_R		0.034
gMVP		0.30

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: rs1042229; hg19: chr19-52249672; COSMIC: COSV59053273; COSMIC: COSV59053273;