chr19-51746507-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002029.4(FPR1):c.488G>A(p.Arg163His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,614,120 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R163C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0058 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 23 hom. )

Consequence

FPR1
NM_002029.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.92

Publications

8 publications found

Variant links:

COSMIC-nc: COSV107354564

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)

FPR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054709613).

BP6

Variant 19-51746507-C-T is Benign according to our data. Variant chr19-51746507-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 456367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 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.488G>A	p.Arg163His	missense	Exon 2 of 2	NP_002020.1	P21462
	FPR1	NM_001193306.2		c.488G>A	p.Arg163His	missense	Exon 3 of 3	NP_001180235.1	P21462

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FPR1	ENST00000304748.5	TSL:1 MANE Select	c.488G>A	p.Arg163His	missense	Exon 2 of 2	ENSP00000302707.3	P21462
FPR1	ENST00000594900.2	TSL:4	c.488G>A	p.Arg163His	missense	Exon 3 of 3	ENSP00000470750.2	P21462
FPR1	ENST00000595042.5	TSL:2	c.488G>A	p.Arg163His	missense	Exon 3 of 3	ENSP00000471493.1	P21462

Frequencies

GnomAD3 genomes

AF:

0.00577

AC:

877

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00928

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00557

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00473

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00414

AC:

1041

AN:

251308

AF XY:

0.00402

show subpopulations

Gnomad AFR exome

AF:

0.00861

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00490

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00424

AC:

6201

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

3030

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0103

AC:

344

AN:

33480

American (AMR)

AF:

0.00405

AC:

181

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00979

AC:

256

AN:

26136

East Asian (EAS)

AF:

0.000202

AC:

AN:

39700

South Asian (SAS)

AF:

0.000939

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00139

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00537

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00444

AC:

4940

AN:

1112006

Other (OTH)

AF:

0.00474

AC:

286

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

411

823

1234

1646

2057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00579

AC:

881

AN:

152232

Hom.:

Cov.:

AF XY:

0.00578

AC XY:

430

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00937

AC:

389

AN:

41520

American (AMR)

AF:

0.00556

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00473

AC:

322

AN:

68022

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

146

195

244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00571

Hom.:

Bravo

AF:

0.00646

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00382

AC:

464

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00545

EpiControl

AF:

0.00539

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

FPR1-related disorder (1)

Gingival disorder (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.59

M_CAP

Benign

0.023

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

PhyloP100

2.9

PrimateAI

Benign

0.25

PROVEAN

Benign

0.37

REVEL

Benign

0.12

Sift

Uncertain

0.021

Sift4G

Benign

0.14

Polyphen

0.68

Vest4

0.17

MVP

0.82

MPC

0.63

ClinPred

0.027

GERP RS

2.6

Varity_R

0.067

gMVP

0.40

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over