rs3816690

Positions:

• chr3-142848188-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.448+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 1,605,068 control chromosomes in the GnomAD database, including 2,776 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 0.056 (249 hom., cov: 33)
  • Exomes 𝑓: 0.056 (2527 hom.)
• Consequence: PCOLCE2 NM_013363.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCOLCE2	NM_013363.4	c.448+29A>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.448+29A>G		intron_variant		1	NM_013363.4	ENSP00000295992	P1

Frequencies

GnomAD3 genomes AF: 0.0562 AC: 8555 AN: 152194 Hom.: 250 Cov.: 33

Gnomad AFR AF: 0.0501

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.0557

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0657

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.0828

GnomAD3 exomes AF: 0.0577 AC: 14357 AN: 248864 Hom.: 471 AF XY: 0.0613 AC XY: 8246 AN XY: 134558

Gnomad AFR exome AF: 0.0488

Gnomad AMR exome AF: 0.0346

Gnomad ASJ exome AF: 0.0727

Gnomad EAS exome AF: 0.0529

Gnomad SAS exome AF: 0.0994

Gnomad FIN exome AF: 0.0673

Gnomad NFE exome AF: 0.0521

Gnomad OTH exome AF: 0.0642

GnomAD4 exome AF: 0.0561 AC: 81494 AN: 1452756 Hom.: 2527 Cov.: 31 AF XY: 0.0578 AC XY: 41717 AN XY: 721244

Gnomad4 AFR exome AF: 0.0476

Gnomad4 AMR exome AF: 0.0382

Gnomad4 ASJ exome AF: 0.0716

Gnomad4 EAS exome AF: 0.0556

Gnomad4 SAS exome AF: 0.0975

Gnomad4 FIN exome AF: 0.0675

Gnomad4 NFE exome AF: 0.0526

Gnomad4 OTH exome AF: 0.0605

GnomAD4 genome AF: 0.0562 AC: 8555 AN: 152312 Hom.: 249 Cov.: 33 AF XY: 0.0573 AC XY: 4269 AN XY: 74480

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.0534

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.0559

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0657

Gnomad4 NFE AF: 0.0538

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0572 Hom.: 355

Bravo AF: 0.0542

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.55

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: rs3816690; hg19: chr3-142567030;