rs7637508

Variant names:

• chr3-142880443-C-T
• rs7637508
• NM_013363.4:c.192+7226G>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.192+7226G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,138 control chromosomes in the GnomAD database, including 3,616 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 0.17 (3616 hom., cov: 31)
• Consequence: PCOLCE2 NM_013363.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCOLCE2	NM_013363.4	c.192+7226G>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.192+7226G>A		intron_variant	Intron 2 of 8	1	NM_013363.4	ENSP00000295992.3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25636 AN: 152020 Hom.: 3597 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0995

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.169 AC: 25691 AN: 152138 Hom.: 3616 Cov.: 31 AF XY: 0.166 AC XY: 12375 AN XY: 74398

African (AFR) AF: 0.390 AC: 16167 AN: 41446

American (AMR) AF: 0.108 AC: 1651 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3466

East Asian (EAS) AF: 0.0152 AC: 79 AN: 5188

South Asian (SAS) AF: 0.102 AC: 491 AN: 4832

European-Finnish (FIN) AF: 0.0995 AC: 1053 AN: 10580

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0793 AC: 5392 AN: 68012

Other (OTH) AF: 0.172 AC: 363 AN: 2114

Alfa AF: 0.103 Hom.: 2148

Bravo AF: 0.178

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.3
DANN	Benign	0.31
PhyloP100		-0.021
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: rs7637508; hg19: chr3-142599285;