rs28930680

Variant names:

• chr19-51746689-A-G
• rs28930680
• NM_002029.4:c.306T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002029.4(FPR1):​c.306T>C​(p.Phe102Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,614,162 control chromosomes in the GnomAD database, including 1,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (109 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1491 hom.)
• Consequence: FPR1 NM_002029.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0970
• Publications: 11 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=-0.92).
• BP6: Variant 19-51746689-A-G is Benign according to our data. Variant chr19-51746689-A-G is described in ClinVar as Benign. ClinVar VariationId is 456365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.097 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0629 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	NM_002029.4	MANE Select	c.306T>C	p.Phe102Phe	synonymous	Exon 2 of 2	NP_002020.1
	FPR1	NM_001193306.2		c.306T>C	p.Phe102Phe	synonymous	Exon 3 of 3	NP_001180235.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	ENST00000304748.5	TSL:1 MANE Select	c.306T>C	p.Phe102Phe	synonymous	Exon 2 of 2	ENSP00000302707.3
	FPR1	ENST00000594900.2	TSL:4	c.306T>C	p.Phe102Phe	synonymous	Exon 3 of 3	ENSP00000470750.2
	FPR1	ENST00000595042.5	TSL:2	c.306T>C	p.Phe102Phe	synonymous	Exon 3 of 3	ENSP00000471493.1

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 4578 AN: 152160 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.00693

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0293

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0217

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0394

Gnomad OTH AF: 0.0368

GnomAD2 exomes AF: 0.0421 AC: 10589 AN: 251370 AF XY: 0.0459

Gnomad AFR exome AF: 0.00597

Gnomad AMR exome AF: 0.0252

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.0151

Gnomad FIN exome AF: 0.0231

Gnomad NFE exome AF: 0.0425

Gnomad OTH exome AF: 0.0567

GnomAD4 exome AF: 0.0398 AC: 58246 AN: 1461884 Hom.: 1491 Cov.: 77 AF XY: 0.0415 AC XY: 30178 AN XY: 727244

African (AFR) AF: 0.00514 AC: 172 AN: 33480

American (AMR) AF: 0.0264 AC: 1181 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3126 AN: 26136

East Asian (EAS) AF: 0.0109 AC: 433 AN: 39700

South Asian (SAS) AF: 0.0809 AC: 6979 AN: 86258

European-Finnish (FIN) AF: 0.0227 AC: 1211 AN: 53420

Middle Eastern (MID) AF: 0.0992 AC: 572 AN: 5768

European-Non Finnish (NFE) AF: 0.0376 AC: 41841 AN: 1112002

Other (OTH) AF: 0.0452 AC: 2731 AN: 60396

GnomAD4 genome AF: 0.0301 AC: 4591 AN: 152278 Hom.: 109 Cov.: 32 AF XY: 0.0299 AC XY: 2224 AN XY: 74462

African (AFR) AF: 0.00691 AC: 287 AN: 41554

American (AMR) AF: 0.0292 AC: 446 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3470

East Asian (EAS) AF: 0.0145 AC: 75 AN: 5174

South Asian (SAS) AF: 0.0690 AC: 333 AN: 4824

European-Finnish (FIN) AF: 0.0217 AC: 231 AN: 10622

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0394 AC: 2679 AN: 68020

Other (OTH) AF: 0.0440 AC: 93 AN: 2112

Alfa AF: 0.0387 Hom.: 260

Bravo AF: 0.0291

Asia WGS AF: 0.0680 AC: 235 AN: 3478

EpiCase AF: 0.0444

EpiControl AF: 0.0506

ClinVar

ClinVar submissions as Germline

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	-0.92
CADD	Benign	0.20
DANN	Benign	0.32
PhyloP100		0.097
Mutation Taster		=100/0	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: rs28930680; hg19: chr19-52249942; COSMIC: COSV59052116; COSMIC: COSV59052116;