Genetic Variant FPR1:p.Thr9Lys (chr19-51746969-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002029.4(FPR1):c.26C>A(p.Thr9Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T9M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FPR1
NM_002029.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

0 publications found

Variant links:

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048847586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FPR1	NM_002029.4 link	c.26C>A	p.Thr9Lys	missense_variant	Exon 2 of 2	ENST00000304748.5	NP_002020.1
FPR1	NM_001193306.2 link	c.26C>A	p.Thr9Lys	missense_variant	Exon 3 of 3		NP_001180235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
FPR1	ENST00000304748.5 link	c.26C>A	p.Thr9Lys	missense_variant	Exon 2 of 2	1	NM_002029.4	ENSP00000302707.3
FPR1	ENST00000594900.2 link	c.26C>A	p.Thr9Lys	missense_variant	Exon 3 of 3	4		ENSP00000470750.2
FPR1	ENST00000595042.5 link	c.26C>A	p.Thr9Lys	missense_variant	Exon 3 of 3	2		ENSP00000471493.1
FPR1	ENST00000600815.2 link	c.26C>A	p.Thr9Lys	missense_variant	Exon 2 of 2	3		ENSP00000472936.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460344

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

86206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110800

Other (OTH)

AF:

0.00

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.70

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.066

T;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.27

.;T;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.049

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;.;.

PhyloP100

-1.1

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.63

.;N;.;.

REVEL

Benign

0.021

Sift

Benign

0.13

.;T;.;.

Sift4G

Benign

0.90

T;T;.;.

Polyphen

0.28

B;B;.;.

Vest4

0.078

MutPred

0.31

Gain of ubiquitination at T9 (P = 0.0022);Gain of ubiquitination at T9 (P = 0.0022);Gain of ubiquitination at T9 (P = 0.0022);Gain of ubiquitination at T9 (P = 0.0022);

MVP

0.15

MPC

0.39

ClinPred

0.14

GERP RS

-2.2

Varity_R

0.032

gMVP

0.19

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over