19-51816862-G-C

Position:

• chr19-51816862-G-C

Variant summary

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

The ENST00000339223.5(FPR3):​c.-10-6877G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,130 control chromosomes in the GnomAD database, including 4,932 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 0.25 (4932 hom., cov: 32)
• Consequence: FPR3 ENST00000339223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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 = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPR3	NM_002030.5	c.-10-6877G>C		intron_variant		ENST00000339223.5	NP_002021.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPR3	ENST00000339223.5	c.-10-6877G>C		intron_variant		1	NM_002030.5	ENSP00000341821	P1
ZNF577	ENST00000638827.1	c.*600-5188C>G		intron_variant, NMD_transcript_variant		5		ENSP00000492704

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37726 AN: 152012 Hom.: 4932 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.248 AC: 37750 AN: 152130 Hom.: 4932 Cov.: 32 AF XY: 0.246 AC XY: 18317 AN XY: 74356

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.285

Alfa AF: 0.126 Hom.: 222

Bravo AF: 0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.53

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: rs10422101; hg19: chr19-52320115;