rs17695224

Positions:

• chr19-51820963-G-A
• chr19-51820963-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002030.5(FPR3):​c.-10-2776G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,162 control chromosomes in the GnomAD database, including 4,416 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4416 hom., cov: 32)
• Consequence: FPR3 NM_002030.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FPR3	NM_002030.5	c.-10-2776G>A		intron_variant		ENST00000339223.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FPR3	ENST00000339223.5	c.-10-2776G>A		intron_variant		1	NM_002030.5	P1
FPR3	ENST00000595991.1	c.-10-2776G>A		intron_variant		4		P1
ZNF577	ENST00000638827.1	c.*600-9289C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35313 AN: 152044 Hom.: 4417 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 35318 AN: 152162 Hom.: 4416 Cov.: 32 AF XY: 0.231 AC XY: 17189 AN XY: 74388

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.266

Alfa AF: 0.263 Hom.: 12394

Bravo AF: 0.239

Asia WGS AF: 0.249 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.59

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: rs17695224; hg19: chr19-52324216;