rs17849971

Positions:

• chr19-51746002-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002029.4(FPR1):​c.993C>T​(p.Thr331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,614,118 control chromosomes in the GnomAD database, including 776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (49 hom., cov: 32)
  • Exomes 𝑓: 0.028 (727 hom.)
• Consequence: FPR1 NM_002029.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.327

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=-0.82).
• BP6: Variant 19-51746002-G-A is Benign according to our data. Variant chr19-51746002-G-A is described in ClinVar as [Benign]. Clinvar id is 402875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.327 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0204 (3102/152246) while in subpopulation NFE AF= 0.0318 (2163/68008). AF 95% confidence interval is 0.0307. There are 49 homozygotes in gnomad4. There are 1515 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FPR1	NM_002029.4	c.993C>T	p.Thr331=	synonymous_variant	2/2	ENST00000304748.5
FPR1	NM_001193306.2	c.993C>T	p.Thr331=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FPR1	ENST00000304748.5	c.993C>T	p.Thr331=	synonymous_variant	2/2	1	NM_002029.4	P1
FPR1	ENST00000594900.2	c.993C>T	p.Thr331=	synonymous_variant	3/3	4		P1
FPR1	ENST00000595042.5	c.993C>T	p.Thr331=	synonymous_variant	3/3	2		P1
FPR1	ENST00000600815.2	c.993C>T	p.Thr331=	synonymous_variant	2/2	3		P1

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3101 AN: 152128 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00582

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0318

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0210 AC: 5283 AN: 251282 Hom.: 89 AF XY: 0.0211 AC XY: 2870 AN XY: 135808

Gnomad AFR exome AF: 0.00560

Gnomad AMR exome AF: 0.00810

Gnomad ASJ exome AF: 0.00933

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00872

Gnomad FIN exome AF: 0.0426

Gnomad NFE exome AF: 0.0308

Gnomad OTH exome AF: 0.0212

GnomAD4 exome AF: 0.0280 AC: 40904 AN: 1461872 Hom.: 727 Cov.: 71 AF XY: 0.0276 AC XY: 20096 AN XY: 727232

Gnomad4 AFR exome AF: 0.00451

Gnomad4 AMR exome AF: 0.00834

Gnomad4 ASJ exome AF: 0.00957

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00878

Gnomad4 FIN exome AF: 0.0398

Gnomad4 NFE exome AF: 0.0321

Gnomad4 OTH exome AF: 0.0257

GnomAD4 genome AF: 0.0204 AC: 3102 AN: 152246 Hom.: 49 Cov.: 32 AF XY: 0.0203 AC XY: 1515 AN XY: 74452

Gnomad4 AFR AF: 0.00580

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.0421

Gnomad4 NFE AF: 0.0318

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0259 Hom.: 42

Bravo AF: 0.0176

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0271

EpiControl AF: 0.0278

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.50

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: rs17849971; hg19: chr19-52249255;