rs5030880

Variant names:

• chr19-51746427-T-A
• rs5030880
• NM_002029.4:c.568A>T

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.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. 14/21 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:4 O:1
• Conservation: PhyloP100: -0.104
• Publications: 46 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=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 VariationId 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 rank	MANE	Protein	UniProt
FPR1	NM_002029.4	c.568A>T	p.Arg190Trp	missense_variant	Exon 2 of 2	ENST00000304748.5	NP_002020.1
FPR1	NM_001193306.2	c.568A>T	p.Arg190Trp	missense_variant	Exon 3 of 3		NP_001180235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FPR1	ENST00000304748.5	c.568A>T	p.Arg190Trp	missense_variant	Exon 2 of 2	1	NM_002029.4	ENSP00000302707.3
FPR1	ENST00000594900.2	c.568A>T	p.Arg190Trp	missense_variant	Exon 3 of 3	4		ENSP00000470750.2
FPR1	ENST00000595042.5	c.568A>T	p.Arg190Trp	missense_variant	Exon 3 of 3	2		ENSP00000471493.1
FPR1	ENST00000600815.2	c.568A>T	p.Arg190Trp	missense_variant	Exon 2 of 2	3		ENSP00000472936.2

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

GnomAD2 exomes AF: 0.133 AC: 33346 AN: 251326 AF XY: 0.136

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 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

African (AFR) AF: 0.0851 AC: 2850 AN: 33480

American (AMR) AF: 0.0876 AC: 3918 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 3121 AN: 26136

East Asian (EAS) AF: 0.160 AC: 6364 AN: 39700

South Asian (SAS) AF: 0.184 AC: 15884 AN: 86258

European-Finnish (FIN) AF: 0.165 AC: 8796 AN: 53412

Middle Eastern (MID) AF: 0.0903 AC: 521 AN: 5768

European-Non Finnish (NFE) AF: 0.126 AC: 140453 AN: 1111982

Other (OTH) AF: 0.134 AC: 8079 AN: 60396

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

African (AFR) AF: 0.0881 AC: 3651 AN: 41462

American (AMR) AF: 0.0994 AC: 1519 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 414 AN: 3464

East Asian (EAS) AF: 0.199 AC: 1025 AN: 5148

South Asian (SAS) AF: 0.180 AC: 866 AN: 4806

European-Finnish (FIN) AF: 0.172 AC: 1813 AN: 10566

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8633 AN: 67954

Other (OTH) AF: 0.127 AC: 268 AN: 2104

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:4 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2 Other:1

Oct 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

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

- -

FPR1 POLYMORPHISM Benign:1

Jan 07, 2025

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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 v4.3

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
LIST_S2	Benign	0.51	.;T;T
MetaRNN	Benign	0.0027	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L;L;.
PhyloP100		-0.10
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.0	.;N;.
REVEL	Benign	0.031
Sift	Uncertain	0.027	.;D;.
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
Mutation Taster		=99/1	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: rs5030880; hg19: chr19-52249680; COSMIC: COSV59051377; COSMIC: COSV59051377;