rs9846406

chr3-142823841-T-C

Variant summary

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

The NM_013363.4(PCOLCE2):c.866-226A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,068 control chromosomes in the GnomAD database, including 11,254 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 0.34 (11254 hom., cov: 32)
• Consequence: PCOLCE2 NM_013363.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

Genes affected

PCOLCE2 (HGNC:8739): (procollagen C-endopeptidase enhancer 2) Enables collagen binding activity; heparin binding activity; and peptidase activator activity. Predicted to be involved in positive regulation of peptidase activity. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in extracellular region. [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=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCOLCE2	NM_013363.4	c.866-226A>G		intron_variant		ENST00000295992.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCOLCE2	ENST00000295992.8	c.866-226A>G		intron_variant		1	NM_013363.4	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52193 AN: 151950 Hom.: 11226 Cov.: 32

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.344 AC: 52275 AN: 152068 Hom.: 11254 Cov.: 32 AF XY: 0.337 AC XY: 25042 AN XY: 74320

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.292

Alfa AF: 0.303 Hom.: 1043

Bravo AF: 0.358

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	11
Dann	Benign	0.78

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: rs9846406; hg19: chr3-142542683;