rs2070745

chr19-51746694-C-Gchr19-51746694-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002029.4(FPR1):c.301G>C(p.Val101Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,613,728 control chromosomes in the GnomAD database, including 114,578 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V101I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.37 (10673 hom., cov: 31)
  • Exomes 𝑓: 0.37 (103905 hom.)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.283

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.5453434E-5).
• BP6: Variant 19-51746694-C-G is Benign according to our data. Variant chr19-51746694-C-G is described in ClinVar as [Benign]. Clinvar id is 402878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FPR1	NM_002029.4	c.301G>C	p.Val101Leu	missense_variant	2/2	ENST00000304748.5
FPR1	NM_001193306.2	c.301G>C	p.Val101Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FPR1	ENST00000304748.5	c.301G>C	p.Val101Leu	missense_variant	2/2	1	NM_002029.4	P1
FPR1	ENST00000594900.2	c.301G>C	p.Val101Leu	missense_variant	3/3	4		P1
FPR1	ENST00000595042.5	c.301G>C	p.Val101Leu	missense_variant	3/3	2		P1
FPR1	ENST00000600815.2	c.301G>C	p.Val101Leu	missense_variant	2/2	3		P1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56191 AN: 151790 Hom.: 10667 Cov.: 31

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.366

GnomAD3 exomes AF: 0.401 AC: 100695 AN: 251342 Hom.: 21697 AF XY: 0.390 AC XY: 52939 AN XY: 135840

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.607

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.476

Gnomad SAS exome AF: 0.347

Gnomad FIN exome AF: 0.436

Gnomad NFE exome AF: 0.358

Gnomad OTH exome AF: 0.383

GnomAD4 exome AF: 0.372 AC: 544174 AN: 1461820 Hom.: 103905 Cov.: 76 AF XY: 0.370 AC XY: 269277 AN XY: 727210

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.593

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.352

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.370 AC: 56221 AN: 151908 Hom.: 10673 Cov.: 31 AF XY: 0.375 AC XY: 27859 AN XY: 74258

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.363

Alfa AF: 0.312 Hom.: 2306

Bravo AF: 0.375

TwinsUK AF: 0.365 AC: 1354

ALSPAC AF: 0.362 AC: 1394

ESP6500AA AF: 0.315 AC: 1389

ESP6500EA AF: 0.358 AC: 3075

ExAC AF: 0.389 AC: 47241

EpiCase AF: 0.350

EpiControl AF: 0.347

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

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: MAF -

Gingival disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Other:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.20
Dann	Benign	0.35
DEOGEN2	Benign	0.049	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.029	N
MetaRNN	Benign	0.000075	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.96	L;L;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.65	T;T;.
Polyphen		0.0010	B;B;.
Vest4		0.019
MPC		0.30
ClinPred		0.0047	T
GERP RS		-2.0
Varity_R		0.084
gMVP		0.33

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: rs2070745; hg19: chr19-52249947; COSMIC: COSV59051261; COSMIC: COSV59051261;