NM_002029.4:c.32T>C

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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I11S) has been classified as Uncertain significance.

• 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

Sel.	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	P21462
	FPR1	NM_001193306.2		c.32T>C	p.Ile11Thr	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.32T>C	p.Ile11Thr	missense	Exon 2 of 2	ENSP00000302707.3	P21462
	FPR1	ENST00000594900.2	TSL:4	c.32T>C	p.Ile11Thr	missense	Exon 3 of 3	ENSP00000470750.2	P21462
	FPR1	ENST00000595042.5	TSL:2	c.32T>C	p.Ile11Thr	missense	Exon 3 of 3	ENSP00000471493.1	P21462

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Gingival disorder (1)
-	-	1	not provided (2)
-	-	1	not specified (1)

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;