19-51746963-A-G

Variant names:

• chr19-51746963-A-G
• rs5030878
• NM_002029.4:c.32T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002029.4(FPR1):​c.32T>C​(p.Ile11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,613,220 control chromosomes in the GnomAD database, including 496,799 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47477 hom., cov: 29)
  • Exomes 𝑓: 0.78 (449322 hom.)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.885
• Publications: 47 publications found

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]

FPR1 Gene-Disease associations (from GenCC):

• susceptibility to localized juvenile periodontitis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.877735E-7).
• BP6: Variant 19-51746963-A-G is Benign according to our data. Variant chr19-51746963-A-G is described in ClinVar as Benign. ClinVar VariationId is 402879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002029.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	NM_002029.4	MANE Select	c.32T>C	p.Ile11Thr	missense	Exon 2 of 2	NP_002020.1
	FPR1	NM_001193306.2		c.32T>C	p.Ile11Thr	missense	Exon 3 of 3	NP_001180235.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	ENST00000304748.5	TSL:1 MANE Select	c.32T>C	p.Ile11Thr	missense	Exon 2 of 2	ENSP00000302707.3
	FPR1	ENST00000594900.2	TSL:4	c.32T>C	p.Ile11Thr	missense	Exon 3 of 3	ENSP00000470750.2
	FPR1	ENST00000595042.5	TSL:2	c.32T>C	p.Ile11Thr	missense	Exon 3 of 3	ENSP00000471493.1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 119956 AN: 151872 Hom.: 47444 Cov.: 29

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.792

GnomAD2 exomes AF: 0.807 AC: 202193 AN: 250618 AF XY: 0.806

Gnomad AFR exome AF: 0.794

Gnomad AMR exome AF: 0.827

Gnomad ASJ exome AF: 0.810

Gnomad EAS exome AF: 0.960

Gnomad FIN exome AF: 0.800

Gnomad NFE exome AF: 0.767

Gnomad OTH exome AF: 0.785

GnomAD4 exome AF: 0.783 AC: 1144305 AN: 1461230 Hom.: 449322 Cov.: 51 AF XY: 0.785 AC XY: 570490 AN XY: 726900

African (AFR) AF: 0.791 AC: 26475 AN: 33460

American (AMR) AF: 0.822 AC: 36731 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 21172 AN: 26128

East Asian (EAS) AF: 0.970 AC: 38503 AN: 39694

South Asian (SAS) AF: 0.854 AC: 73620 AN: 86242

European-Finnish (FIN) AF: 0.803 AC: 42898 AN: 53414

Middle Eastern (MID) AF: 0.760 AC: 4363 AN: 5742

European-Non Finnish (NFE) AF: 0.768 AC: 853173 AN: 1111486

Other (OTH) AF: 0.785 AC: 47370 AN: 60378

GnomAD4 genome AF: 0.790 AC: 120039 AN: 151990 Hom.: 47477 Cov.: 29 AF XY: 0.793 AC XY: 58945 AN XY: 74296

African (AFR) AF: 0.788 AC: 32633 AN: 41402

American (AMR) AF: 0.797 AC: 12188 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2791 AN: 3470

East Asian (EAS) AF: 0.964 AC: 4968 AN: 5152

South Asian (SAS) AF: 0.869 AC: 4186 AN: 4816

European-Finnish (FIN) AF: 0.797 AC: 8420 AN: 10568

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52170 AN: 67980

Other (OTH) AF: 0.786 AC: 1660 AN: 2112

Alfa AF: 0.777 Hom.: 202139

Bravo AF: 0.789

TwinsUK AF: 0.771 AC: 2858

ALSPAC AF: 0.774 AC: 2983

ESP6500AA AF: 0.792 AC: 3488

ESP6500EA AF: 0.763 AC: 6559

ExAC AF: 0.804 AC: 97618

Asia WGS AF: 0.851 AC: 2959 AN: 3478

EpiCase AF: 0.764

EpiControl AF: 0.769

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

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

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.

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0050
DANN	Benign	0.49
DEOGEN2	Benign	0.066	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00082	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	7.9e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.89
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.030
Sift	Benign	0.63	T
Sift4G	Benign	0.77	T
Polyphen		0.0080	B
Vest4		0.010
MPC		0.38
ClinPred		0.0061	T
GERP RS		-6.9
Varity_R		0.041
gMVP		0.097
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5030878; hg19: chr19-52250216; COSMIC: COSV107354432;