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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	NM_002029.4	MANE Select	c.568A>T	p.Arg190Trp	missense	Exon 2 of 2	NP_002020.1	P21462
	FPR1	NM_001193306.2		c.568A>T	p.Arg190Trp	missense	Exon 3 of 3	NP_001180235.1	P21462

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	ENST00000304748.5	TSL:1 MANE Select	c.568A>T	p.Arg190Trp	missense	Exon 2 of 2	ENSP00000302707.3	P21462
	FPR1	ENST00000594900.2	TSL:4	c.568A>T	p.Arg190Trp	missense	Exon 3 of 3	ENSP00000470750.2	P21462
	FPR1	ENST00000595042.5	TSL:2	c.568A>T	p.Arg190Trp	missense	Exon 3 of 3	ENSP00000471493.1	P21462

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (3)
-	-	1	FPR1 POLYMORPHISM (1)
-	-	1	Gingival disorder (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	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
Polyphen		0.0020	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;