3-142857613-C-T

Variant names:

• chr3-142857613-C-T
• rs6440116
• NM_013363.4:c.193-9141G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013363.4(PCOLCE2):​c.193-9141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,064 control chromosomes in the GnomAD database, including 28,649 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 0.61 (28649 hom., cov: 32)
• Consequence: PCOLCE2 NM_013363.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCOLCE2	NM_013363.4	c.193-9141G>A		intron_variant	Intron 2 of 8	ENST00000295992.8	NP_037495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCOLCE2	ENST00000295992.8	c.193-9141G>A		intron_variant	Intron 2 of 8	1	NM_013363.4	ENSP00000295992.3
PCOLCE2	ENST00000648195.1	c.193-9141G>A		intron_variant	Intron 2 of 8			ENSP00000497763.1
PCOLCE2	ENST00000485766.1	c.193-9141G>A		intron_variant	Intron 2 of 6	5		ENSP00000419842.1
PCOLCE2	ENST00000495732.5	n.358-9141G>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92585 AN: 151946 Hom.: 28627 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.609 AC: 92659 AN: 152064 Hom.: 28649 Cov.: 32 AF XY: 0.606 AC XY: 45061 AN XY: 74332

African (AFR) AF: 0.569 AC: 23572 AN: 41448

American (AMR) AF: 0.539 AC: 8244 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2336 AN: 3472

East Asian (EAS) AF: 0.343 AC: 1769 AN: 5164

South Asian (SAS) AF: 0.465 AC: 2240 AN: 4822

European-Finnish (FIN) AF: 0.698 AC: 7376 AN: 10574

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 45011 AN: 67980

Other (OTH) AF: 0.632 AC: 1334 AN: 2112

Alfa AF: 0.638 Hom.: 129049

Bravo AF: 0.596

Asia WGS AF: 0.434 AC: 1510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.19
PhyloP100		-0.038
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6440116; hg19: chr3-142576455;