rs142210016

chr19-51746189-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002029.4(FPR1):c.806G>A(p.Arg269His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,614,112 control chromosomes in the GnomAD database, including 3 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R269C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (2 hom.)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.70

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038508475).
• BP6: Variant 19-51746189-C-T is Benign according to our data. Variant chr19-51746189-C-T is described in ClinVar as [Benign]. Clinvar id is 526511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FPR1	NM_002029.4	c.806G>A	p.Arg269His	missense_variant	2/2	ENST00000304748.5
FPR1	NM_001193306.2	c.806G>A	p.Arg269His	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FPR1	ENST00000304748.5	c.806G>A	p.Arg269His	missense_variant	2/2	1	NM_002029.4	P1
FPR1	ENST00000594900.2	c.806G>A	p.Arg269His	missense_variant	3/3	4		P1
FPR1	ENST00000595042.5	c.806G>A	p.Arg269His	missense_variant	3/3	2		P1
FPR1	ENST00000600815.2	c.806G>A	p.Arg269His	missense_variant	2/2	3		P1

Frequencies

GnomAD3 genomes AF: 0.00343 AC: 522 AN: 152120 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

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: 0.0000882

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00102 AC: 256 AN: 250746 Hom.: 2 AF XY: 0.000767 AC XY: 104 AN XY: 135530

Gnomad AFR exome AF: 0.0134

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.0000972

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000495 AC: 723 AN: 1461874 Hom.: 2 Cov.: 72 AF XY: 0.000418 AC XY: 304 AN XY: 727240

Gnomad4 AFR exome AF: 0.0140

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.000135

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.00345 AC: 525 AN: 152238 Hom.: 1 Cov.: 32 AF XY: 0.00326 AC XY: 243 AN XY: 74468

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000800 Hom.: 0

Bravo AF: 0.00417

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0136 AC: 60

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00124 AC: 151

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Gingival disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

FPR1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 01, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.32
Dann	Benign	0.71
DEOGEN2	Benign	0.041	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.027	N
MetaRNN	Benign	0.0039	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.70	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
Sift4G	Benign	0.33	T;T
Polyphen		0.0040	B;B
Vest4		0.049
MVP		0.45
MPC		0.38
ClinPred		0.00073	T
GERP RS		-5.0
Varity_R		0.025
gMVP		0.15

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: rs142210016; hg19: chr19-52249442;