rs142210016

Variant names:

• chr19-51746189-C-T
• rs142210016
• NM_002029.4:c.806G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002029.4(FPR1):​c.806G>A​(p.Arg269His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,614,112 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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. R269C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (2 hom.)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.70
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038508475).
• BP6: Variant 19-51746189-C-T is Benign according to our data. Variant chr19-51746189-C-T is described in ClinVar as Benign. ClinVar VariationId is 526511.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR,Unknown gene

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.806G>A	p.Arg269His	missense	Exon 2 of 2	NP_002020.1	P21462
	FPR1	NM_001193306.2		c.806G>A	p.Arg269His	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.806G>A	p.Arg269His	missense	Exon 2 of 2	ENSP00000302707.3	P21462
	FPR1	ENST00000594900.2	TSL:4	c.806G>A	p.Arg269His	missense	Exon 3 of 3	ENSP00000470750.2	P21462
	FPR1	ENST00000595042.5	TSL:2	c.806G>A	p.Arg269His	missense	Exon 3 of 3	ENSP00000471493.1	P21462

Frequencies

GnomAD3 genomes AF: 0.00343 AC: 522 AN: 152120 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00102 AC: 256 AN: 250746 AF XY: 0.000767

Gnomad AFR exome AF: 0.0134

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.0000972

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000495 AC: 723 AN: 1461874 Hom.: 2 Cov.: 72 AF XY: 0.000418 AC XY: 304 AN XY: 727240

African (AFR) AF: 0.0140 AC: 468 AN: 33480

American (AMR) AF: 0.000604 AC: 27 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86256

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53416

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000135 AC: 150 AN: 1112002

Other (OTH) AF: 0.00104 AC: 63 AN: 60396

GnomAD4 genome AF: 0.00345 AC: 525 AN: 152238 Hom.: 1 Cov.: 32 AF XY: 0.00326 AC XY: 243 AN XY: 74468

African (AFR) AF: 0.0120 AC: 497 AN: 41524

American (AMR) AF: 0.00118 AC: 18 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68014

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00159 Hom.: 3

Bravo AF: 0.00417

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0136 AC: 60

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00124 AC: 151

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	FPR1-related disorder (1)
-	-	1	Gingival disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.32
DANN	Benign	0.71
DEOGEN2	Benign	0.041	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.70	N
PhyloP100		-1.7
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.12
Sift	Benign	0.15	T
Sift4G	Benign	0.33	T
Polyphen		0.0040	B
Vest4		0.049
MVP		0.45
MPC		0.38
ClinPred		0.00073	T
GERP RS		-5.0
Varity_R		0.025
gMVP		0.15
Mutation Taster		=100/0	polymorphism

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: rs142210016; hg19: chr19-52249442;