rs7637508

Positions:

• chr3-142880443-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.79).
• 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/exons	MANE	UniProt
PCOLCE2	NM_013363.4	c.192+7226G>A		intron_variant		ENST00000295992.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCOLCE2	ENST00000295992.8	c.192+7226G>A		intron_variant		1	NM_013363.4	P1

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

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0152

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0995

Gnomad4 NFE AF: 0.0793

Gnomad4 OTH AF: 0.172

Alfa AF: 0.0925 Hom.: 1281

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

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: rs7637508; hg19: chr3-142599285;