rs761856901

Variant names:

• chr19-51823977-A-G
• rs761856901
• NM_002030.5:c.229A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002030.5(FPR3):​c.229A>G​(p.Ile77Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: FPR3 NM_002030.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28
• Publications: 0 publications found

Genes affected

FPR3 (HGNC:3828): (formyl peptide receptor 3) Predicted to enable N-formyl peptide receptor activity and complement receptor activity. Predicted to be involved in several processes, including complement receptor mediated signaling pathway; phospholipase C-activating G protein-coupled receptor signaling pathway; and positive regulation of cytosolic calcium ion concentration. Predicted to act upstream of or within G protein-coupled receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ZNF577 (HGNC:28673): (zinc finger protein 577) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1255905).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002030.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR3	NM_002030.5	MANE Select	c.229A>G	p.Ile77Val	missense	Exon 2 of 2	NP_002021.3
	ZNF577	NR_163433.1		n.2153-10000T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR3	ENST00000339223.5	TSL:1 MANE Select	c.229A>G	p.Ile77Val	missense	Exon 2 of 2	ENSP00000341821.3	P25089
	FPR3	ENST00000595991.1	TSL:4	c.229A>G	p.Ile77Val	missense	Exon 2 of 2	ENSP00000470471.1	P25089
	FPR3	ENST00000901092.1		c.229A>G	p.Ile77Val	missense	Exon 2 of 2	ENSP00000571151.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251090 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461804 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727198

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.000425 AC: 19 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.89
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.51	N
PhyloP100		3.3
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.14
Sift	Benign	0.26	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.040
MutPred		0.57		Loss of catalytic residue at P79 (P = 0.0303)
MVP		0.49
MPC		0.23
ClinPred		0.055	T
GERP RS		0.96
Varity_R		0.051
gMVP		0.20
Mutation Taster		=98/2	polymorphism

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: rs761856901; hg19: chr19-52327230;