2-37368382-A-G

Position:

• chr2-37368382-A-G

Variant summary

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

The NM_012413.4(QPCT):​c.723+974A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 181,856 control chromosomes in the GnomAD database, including 3,215 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 0.18 (2613 hom., cov: 26)
  • Exomes 𝑓: 0.14 (602 hom.)
• Consequence: QPCT NM_012413.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

Genes affected

QPCT (HGNC:9753): (glutaminyl-peptide cyclotransferase) This gene encodes human pituitary glutaminyl cyclase, which is responsible for the presence of pyroglutamyl residues in many neuroendocrine peptides. The amino acid sequence of this enzyme is 86% identical to that of bovine glutaminyl cyclase. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QPCT	NM_012413.4	c.723+974A>G		intron_variant		ENST00000338415.8	NP_036545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QPCT	ENST00000338415.8	c.723+974A>G		intron_variant		1	NM_012413.4	ENSP00000344829	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 25058 AN: 137650 Hom.: 2612 Cov.: 26

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0938

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.138 AC: 6091 AN: 44156 Hom.: 602 Cov.: 0 AF XY: 0.148 AC XY: 3704 AN XY: 25018

Gnomad4 AFR exome AF: 0.181

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.0913

Gnomad4 EAS exome AF: 0.532

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.182 AC: 25080 AN: 137700 Hom.: 2613 Cov.: 26 AF XY: 0.189 AC XY: 12297 AN XY: 65144

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.0938

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.188

Alfa AF: 0.133 Hom.: 1726

Bravo AF: 0.179

Asia WGS AF: 0.391 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.35

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: rs3770748; hg19: chr2-37595525;