19-51746419-A-C

Variant names:

• chr19-51746419-A-C
• rs1042229
• NM_002029.4:c.576T>G

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.576T>G​(p.Asn192Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,613,830 control chromosomes in the GnomAD database, including 91,883 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 (★★). Synonymous variant affecting the same amino acid position (i.e. N192N) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.36 (10311 hom., cov: 31)
  • Exomes 𝑓: 0.33 (81572 hom.)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.296
• Publications: 52 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=0.0011065602).
• BP6: Variant 19-51746419-A-C is Benign according to our data. Variant chr19-51746419-A-C is described in ClinVar as Benign. ClinVar VariationId is 402876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 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.576T>G	p.Asn192Lys	missense	Exon 2 of 2	NP_002020.1
	FPR1	NM_001193306.2		c.576T>G	p.Asn192Lys	missense	Exon 3 of 3	NP_001180235.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	ENST00000304748.5	TSL:1 MANE Select	c.576T>G	p.Asn192Lys	missense	Exon 2 of 2	ENSP00000302707.3
	FPR1	ENST00000594900.2	TSL:4	c.576T>G	p.Asn192Lys	missense	Exon 3 of 3	ENSP00000470750.2
	FPR1	ENST00000595042.5	TSL:2	c.576T>G	p.Asn192Lys	missense	Exon 3 of 3	ENSP00000471493.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54938 AN: 151860 Hom.: 10298 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.376

GnomAD2 exomes AF: 0.319 AC: 80159 AN: 251308 AF XY: 0.321

Gnomad AFR exome AF: 0.464

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.279

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.331 AC: 484143 AN: 1461852 Hom.: 81572 Cov.: 70 AF XY: 0.331 AC XY: 241038 AN XY: 727238

African (AFR) AF: 0.472 AC: 15809 AN: 33480

American (AMR) AF: 0.230 AC: 10295 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 9017 AN: 26136

East Asian (EAS) AF: 0.329 AC: 13047 AN: 39700

South Asian (SAS) AF: 0.318 AC: 27396 AN: 86258

European-Finnish (FIN) AF: 0.293 AC: 15666 AN: 53412

Middle Eastern (MID) AF: 0.434 AC: 2506 AN: 5768

European-Non Finnish (NFE) AF: 0.332 AC: 369703 AN: 1111980

Other (OTH) AF: 0.343 AC: 20704 AN: 60394

GnomAD4 genome AF: 0.362 AC: 54982 AN: 151978 Hom.: 10311 Cov.: 31 AF XY: 0.359 AC XY: 26692 AN XY: 74300

African (AFR) AF: 0.461 AC: 19096 AN: 41432

American (AMR) AF: 0.301 AC: 4605 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1221 AN: 3464

East Asian (EAS) AF: 0.300 AC: 1539 AN: 5136

South Asian (SAS) AF: 0.319 AC: 1535 AN: 4814

European-Finnish (FIN) AF: 0.295 AC: 3118 AN: 10572

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22496 AN: 67958

Other (OTH) AF: 0.373 AC: 786 AN: 2110

Alfa AF: 0.461 Hom.: 41618

TwinsUK AF: 0.337 AC: 1248

ALSPAC AF: 0.333 AC: 1282

ESP6500AA AF: 0.506 AC: 2231

ESP6500EA AF: 0.396 AC: 3403

ExAC AF: 0.327 AC: 39638

EpiCase AF: 0.350

EpiControl AF: 0.348

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.20
DANN	Benign	0.16
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.97	N
PhyloP100		0.30
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.044
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.016
MutPred		0.32		Gain of methylation at N192 (P = 0.0076)
MPC		0.35
ClinPred		0.00026	T
GERP RS		1.5
Varity_R		0.034
gMVP		0.30
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: rs1042229; hg19: chr19-52249672; COSMIC: COSV59053273; COSMIC: COSV59053273;