NM_002029.4:c.1037A>C

Variant names:

• chr19-51745958-T-G
• rs867228
• NM_002029.4:c.1037A>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.1037A>C​(p.Glu346Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,609,306 control chromosomes in the GnomAD database, including 517,360 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. E346E) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.80 (48125 hom., cov: 30)
  • Exomes 𝑓: 0.80 (469235 hom.)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: 1.10
• Publications: 79 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=1.0961179E-6).
• BP6: Variant 19-51745958-T-G is Benign according to our data. Variant chr19-51745958-T-G is described in ClinVar as Benign. ClinVar VariationId is 402874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.822 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.1037A>C	p.Glu346Ala	missense	Exon 2 of 2	NP_002020.1	P21462
	FPR1	NM_001193306.2		c.1037A>C	p.Glu346Ala	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.1037A>C	p.Glu346Ala	missense	Exon 2 of 2	ENSP00000302707.3	P21462
	FPR1	ENST00000594900.2	TSL:4	c.1037A>C	p.Glu346Ala	missense	Exon 3 of 3	ENSP00000470750.2	P21462
	FPR1	ENST00000595042.5	TSL:2	c.1037A>C	p.Glu346Ala	missense	Exon 3 of 3	ENSP00000471493.1	P21462

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120916 AN: 151898 Hom.: 48097 Cov.: 30

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.785

GnomAD2 exomes AF: 0.803 AC: 201532 AN: 251018 AF XY: 0.804

Gnomad AFR exome AF: 0.791

Gnomad AMR exome AF: 0.851

Gnomad ASJ exome AF: 0.785

Gnomad EAS exome AF: 0.705

Gnomad FIN exome AF: 0.773

Gnomad NFE exome AF: 0.801

Gnomad OTH exome AF: 0.801

GnomAD4 exome AF: 0.802 AC: 1168580 AN: 1457290 Hom.: 469235 Cov.: 50 AF XY: 0.804 AC XY: 581712 AN XY: 723872

African (AFR) AF: 0.794 AC: 26504 AN: 33388

American (AMR) AF: 0.847 AC: 37808 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 20584 AN: 26102

East Asian (EAS) AF: 0.721 AC: 28498 AN: 39552

South Asian (SAS) AF: 0.852 AC: 73447 AN: 86212

European-Finnish (FIN) AF: 0.782 AC: 41755 AN: 53380

Middle Eastern (MID) AF: 0.824 AC: 4737 AN: 5750

European-Non Finnish (NFE) AF: 0.801 AC: 887198 AN: 1108064

Other (OTH) AF: 0.798 AC: 48049 AN: 60192

GnomAD4 genome AF: 0.796 AC: 120992 AN: 152016 Hom.: 48125 Cov.: 30 AF XY: 0.796 AC XY: 59098 AN XY: 74270

African (AFR) AF: 0.790 AC: 32779 AN: 41488

American (AMR) AF: 0.810 AC: 12364 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2746 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3697 AN: 5154

South Asian (SAS) AF: 0.844 AC: 4070 AN: 4822

European-Finnish (FIN) AF: 0.777 AC: 8195 AN: 10552

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54456 AN: 67966

Other (OTH) AF: 0.780 AC: 1639 AN: 2102

Alfa AF: 0.799 Hom.: 110602

Bravo AF: 0.798

TwinsUK AF: 0.799 AC: 2961

ALSPAC AF: 0.799 AC: 3078

ESP6500AA AF: 0.793 AC: 3495

ESP6500EA AF: 0.799 AC: 6870

ExAC AF: 0.804 AC: 97639

Asia WGS AF: 0.721 AC: 2507 AN: 3478

EpiCase AF: 0.801

EpiControl AF: 0.797

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	0.082
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.1
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.15
Sift	Benign	0.069	T
Sift4G	Uncertain	0.014	D
Polyphen		0.65	P
Vest4		0.066
MPC		0.34
ClinPred		0.033	T
GERP RS		3.1
Varity_R		0.14
gMVP		0.18
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: rs867228; hg19: chr19-52249211; COSMIC: COSV59054086; COSMIC: COSV59054086;