19-51746706-G-T

Position:

• chr19-51746706-G-T

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.289C>A​(p.Leu97Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,614,132 control chromosomes in the GnomAD database, including 175 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (14 hom., cov: 31)
  • Exomes 𝑓: 0.0041 (161 hom.)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.557

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=0.0040761232).
• BP6: Variant 19-51746706-G-T is Benign according to our data. Variant chr19-51746706-G-T is described in ClinVar as [Benign]. Clinvar id is 526514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-51746706-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPR1	NM_002029.4	c.289C>A	p.Leu97Met	missense_variant	2/2	ENST00000304748.5	NP_002020.1
FPR1	NM_001193306.2	c.289C>A	p.Leu97Met	missense_variant	3/3		NP_001180235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPR1	ENST00000304748.5	c.289C>A	p.Leu97Met	missense_variant	2/2	1	NM_002029.4	ENSP00000302707.3
FPR1	ENST00000594900.2	c.289C>A	p.Leu97Met	missense_variant	3/3	4		ENSP00000470750.2
FPR1	ENST00000595042.5	c.289C>A	p.Leu97Met	missense_variant	3/3	2		ENSP00000471493.1
FPR1	ENST00000600815.2	c.289C>A	p.Leu97Met	missense_variant	2/2	3		ENSP00000472936.2

Frequencies

GnomAD3 genomes AF: 0.00464 AC: 706 AN: 152130 Hom.: 16 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00862 AC: 2167 AN: 251396 Hom.: 67 AF XY: 0.00832 AC XY: 1131 AN XY: 135872

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00337

Gnomad EAS exome AF: 0.0746

Gnomad SAS exome AF: 0.00349

Gnomad FIN exome AF: 0.0188

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.00782

GnomAD4 exome AF: 0.00408 AC: 5968 AN: 1461884 Hom.: 161 Cov.: 76 AF XY: 0.00416 AC XY: 3022 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00371

Gnomad4 EAS exome AF: 0.0890

Gnomad4 SAS exome AF: 0.00394

Gnomad4 FIN exome AF: 0.0173

Gnomad4 NFE exome AF: 0.000700

Gnomad4 OTH exome AF: 0.00472

GnomAD4 genome AF: 0.00460 AC: 701 AN: 152248 Hom.: 14 Cov.: 31 AF XY: 0.00594 AC XY: 442 AN XY: 74428

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.0774

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0189

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00111 Hom.: 1

Bravo AF: 0.00383

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.00869 AC: 1055

Asia WGS AF: 0.0270 AC: 93 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Gingival disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 23, 2024

- -

FPR1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 2019

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). -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T;T;.
Eigen	Benign	0.048
Eigen_PC	Benign	-0.044
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.68	.;T;T
MetaRNN	Benign	0.0041	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.61	N;N;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.73	.;N;.
REVEL	Benign	0.16
Sift	Benign	0.21	.;T;.
Sift4G	Benign	0.39	T;T;.
Polyphen		0.95	P;P;.
Vest4		0.19
MVP		0.76
MPC		0.77
ClinPred		0.044	T
GERP RS		2.5
Varity_R		0.10
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs78488639; hg19: chr19-52249959;