rs6788089

Positions:

• chr3-142875113-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.192+12556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 152,226 control chromosomes in the GnomAD database, including 659 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 0.081 (659 hom., cov: 32)
• Consequence: PCOLCE2 NM_013363.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCOLCE2	NM_013363.4	c.192+12556A>G		intron_variant		ENST00000295992.8	NP_037495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCOLCE2	ENST00000295992.8	c.192+12556A>G		intron_variant		1	NM_013363.4	ENSP00000295992	P1

Frequencies

GnomAD3 genomes AF: 0.0808 AC: 12290 AN: 152108 Hom.: 659 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0854

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0865

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0807 AC: 12290 AN: 152226 Hom.: 659 Cov.: 32 AF XY: 0.0777 AC XY: 5780 AN XY: 74426

Gnomad4 AFR AF: 0.0215

Gnomad4 AMR AF: 0.0853

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0245

Gnomad4 FIN AF: 0.0865

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.100

Alfa AF: 0.106 Hom.: 554

Bravo AF: 0.0800

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.75

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: rs6788089; hg19: chr3-142593955;