rs148095693

Positions:

• chr19-51746969-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002029.4(FPR1):​c.26C>T​(p.Thr9Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000754 in 1,612,534 control chromosomes in the GnomAD database, including 9 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (3 hom., cov: 30)
  • Exomes 𝑓: 0.00061 (6 hom.)
• Consequence: FPR1 NM_002029.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.11

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040142834).
• BP6: Variant 19-51746969-G-A is Benign according to our data. Variant chr19-51746969-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 456364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-51746969-G-A is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPR1	NM_002029.4	c.26C>T	p.Thr9Met	missense_variant	2/2	ENST00000304748.5	NP_002020.1
FPR1	NM_001193306.2	c.26C>T	p.Thr9Met	missense_variant	3/3		NP_001180235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPR1	ENST00000304748.5	c.26C>T	p.Thr9Met	missense_variant	2/2	1	NM_002029.4	ENSP00000302707	P1
FPR1	ENST00000594900.2	c.26C>T	p.Thr9Met	missense_variant	3/3	4		ENSP00000470750	P1
FPR1	ENST00000595042.5	c.26C>T	p.Thr9Met	missense_variant	3/3	2		ENSP00000471493	P1
FPR1	ENST00000600815.2	c.26C>T	p.Thr9Met	missense_variant	2/2	3		ENSP00000472936	P1

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 313 AN: 152076 Hom.: 2 Cov.: 30

Gnomad AFR AF: 0.00546

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000987 AC: 247 AN: 250352 Hom.: 2 AF XY: 0.000924 AC XY: 125 AN XY: 135270

Gnomad AFR exome AF: 0.00628

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000513

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.000612 AC: 894 AN: 1460340 Hom.: 6 Cov.: 34 AF XY: 0.000596 AC XY: 433 AN XY: 726242

Gnomad4 AFR exome AF: 0.00586

Gnomad4 AMR exome AF: 0.00226

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000499

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000390

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome AF: 0.00212 AC: 322 AN: 152194 Hom.: 3 Cov.: 30 AF XY: 0.00187 AC XY: 139 AN XY: 74418

Gnomad4 AFR AF: 0.00556

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.000707 Hom.: 0

Bravo AF: 0.00250

ESP6500AA AF: 0.00477 AC: 21

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00105 AC: 127

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000773

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Gingival disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.2
DANN	Benign	0.27
DEOGEN2	Benign	0.056	T;T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Benign	0.34	.;T;T;T
MetaRNN	Benign	0.0040	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;N;.;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.33	.;N;.;.
REVEL	Benign	0.013
Sift	Benign	0.13	.;T;.;.
Sift4G	Benign	0.12	T;T;.;.
Polyphen		0.066	B;B;.;.
Vest4		0.039
MVP		0.14
MPC		0.31
ClinPred		0.00045	T
GERP RS		-2.2
Varity_R		0.014
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148095693; hg19: chr19-52250222;