rs149382837

Variant names:

• chr19-51746878-G-A
• rs149382837
• NM_002029.4:c.117C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002029.4(FPR1):​c.117C>T​(p.Leu39Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00098 in 1,614,116 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00093 (24 hom.)
• Consequence: FPR1 NM_002029.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.702
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-51746878-G-A is Benign according to our data. Variant chr19-51746878-G-A is described in ClinVar as Benign. ClinVar VariationId is 526510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.702 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00147 (224/152230) while in subpopulation EAS AF = 0.0322 (167/5180). AF 95% confidence interval is 0.0282. There are 3 homozygotes in GnomAd4. There are 121 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• 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.117C>T	p.Leu39Leu	synonymous	Exon 2 of 2	NP_002020.1	P21462
	FPR1	NM_001193306.2		c.117C>T	p.Leu39Leu	synonymous	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.117C>T	p.Leu39Leu	synonymous	Exon 2 of 2	ENSP00000302707.3	P21462
	FPR1	ENST00000594900.2	TSL:4	c.117C>T	p.Leu39Leu	synonymous	Exon 3 of 3	ENSP00000470750.2	P21462
	FPR1	ENST00000595042.5	TSL:2	c.117C>T	p.Leu39Leu	synonymous	Exon 3 of 3	ENSP00000471493.1	P21462

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 227 AN: 152110 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00293 AC: 737 AN: 251424 AF XY: 0.00278

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0317

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.000929 AC: 1358 AN: 1461886 Hom.: 24 Cov.: 76 AF XY: 0.000934 AC XY: 679 AN XY: 727244

African (AFR) AF: 0.000418 AC: 14 AN: 33480

American (AMR) AF: 0.000268 AC: 12 AN: 44724

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

East Asian (EAS) AF: 0.0193 AC: 765 AN: 39698

South Asian (SAS) AF: 0.00299 AC: 258 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1112008

Other (OTH) AF: 0.00430 AC: 260 AN: 60396

GnomAD4 genome AF: 0.00147 AC: 224 AN: 152230 Hom.: 3 Cov.: 31 AF XY: 0.00163 AC XY: 121 AN XY: 74434

African (AFR) AF: 0.000554 AC: 23 AN: 41534

American (AMR) AF: 0.000196 AC: 3 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0322 AC: 167 AN: 5180

South Asian (SAS) AF: 0.00478 AC: 23 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.000409 Hom.: 2

Bravo AF: 0.00131

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.16
DANN	Benign	0.65
PhyloP100		-0.70
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: rs149382837; hg19: chr19-52250131;