rs2287019

Positions:

• chr19-45698914-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017659.4(QPCTL):​c.886+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,609,272 control chromosomes in the GnomAD database, including 27,140 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 (2220 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24920 hom.)
• Consequence: QPCTL NM_017659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

Genes affected

QPCTL (HGNC:25952): (glutaminyl-peptide cyclotransferase like) Enables glutaminyl-peptide cyclotransferase activity and zinc ion binding activity. Acts upstream of or within peptidyl-pyroglutamic acid biosynthetic process, using glutaminyl-peptide cyclotransferase. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

QPCTL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QPCTL	NM_017659.4	c.886+14C>T		intron_variant		ENST00000012049.10	NP_060129.2
QPCTL	NM_001163377.2	c.604+14C>T		intron_variant			NP_001156849.1
QPCTL	XM_047438997.1	c.786+215C>T		intron_variant			XP_047294953.1
QPCTL	XM_017026900.2	c.*127C>T		downstream_gene_variant			XP_016882389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QPCTL	ENST00000012049.10	c.886+14C>T		intron_variant		2	NM_017659.4	ENSP00000012049.4

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25096 AN: 151594 Hom.: 2223 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.188

GnomAD3 exomes AF: 0.173 AC: 43463 AN: 250616 Hom.: 4020 AF XY: 0.175 AC XY: 23769 AN XY: 135566

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.0926

Gnomad ASJ exome AF: 0.283

Gnomad EAS exome AF: 0.193

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.203

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.182 AC: 265307 AN: 1457568 Hom.: 24920 Cov.: 32 AF XY: 0.182 AC XY: 131947 AN XY: 725416

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.0975

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.165 AC: 25101 AN: 151704 Hom.: 2220 Cov.: 31 AF XY: 0.164 AC XY: 12130 AN XY: 74146

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.188

Alfa AF: 0.189 Hom.: 6314

Bravo AF: 0.157

Asia WGS AF: 0.164 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.097
DANN	Benign	0.45

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: rs2287019; hg19: chr19-46202172; COSMIC: COSV50003567; COSMIC: COSV50003567;