chr19-51746449-G-T

Position:

• chr19-51746449-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002029.4(FPR1):​c.546C>A​(p.Pro182Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,844 control chromosomes in the GnomAD database, including 74,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7316 hom., cov: 31)
  • Exomes 𝑓: 0.30 (67631 hom.)
• Consequence: FPR1 NM_002029.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.164

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 19-51746449-G-T is Benign according to our data. Variant chr19-51746449-G-T is described in ClinVar as [Benign]. Clinvar id is 402877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.164 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPR1	NM_002029.4	c.546C>A	p.Pro182Pro	synonymous_variant	2/2	ENST00000304748.5	NP_002020.1
FPR1	NM_001193306.2	c.546C>A	p.Pro182Pro	synonymous_variant	3/3		NP_001180235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPR1	ENST00000304748.5	c.546C>A	p.Pro182Pro	synonymous_variant	2/2	1	NM_002029.4	ENSP00000302707.3
FPR1	ENST00000594900.2	c.546C>A	p.Pro182Pro	synonymous_variant	3/3	4		ENSP00000470750.2
FPR1	ENST00000595042.5	c.546C>A	p.Pro182Pro	synonymous_variant	3/3	2		ENSP00000471493.1
FPR1	ENST00000600815.2	c.546C>A	p.Pro182Pro	synonymous_variant	2/2	3		ENSP00000472936.2

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46757 AN: 151862 Hom.: 7306 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.283

GnomAD3 exomes AF: 0.338 AC: 85060 AN: 251310 Hom.: 15563 AF XY: 0.330 AC XY: 44783 AN XY: 135816

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.505

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.487

Gnomad SAS exome AF: 0.331

Gnomad FIN exome AF: 0.298

Gnomad NFE exome AF: 0.280

Gnomad OTH exome AF: 0.301

GnomAD4 exome AF: 0.299 AC: 437211 AN: 1461864 Hom.: 67631 Cov.: 76 AF XY: 0.299 AC XY: 217178 AN XY: 727236

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.480

Gnomad4 SAS exome AF: 0.324

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.308 AC: 46797 AN: 151980 Hom.: 7316 Cov.: 31 AF XY: 0.309 AC XY: 22928 AN XY: 74284

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.287

Alfa AF: 0.289 Hom.: 11634

Bravo AF: 0.318

Asia WGS AF: 0.393 AC: 1363 AN: 3478

EpiCase AF: 0.270

EpiControl AF: 0.270

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1 Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Gingival disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.8
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs2070746; hg19: chr19-52249702; COSMIC: COSV59054342; COSMIC: COSV59054342;