2-37365485-C-T

Variant names:

• chr2-37365485-C-T
• rs2373000
• NM_012413.4:c.547-1747C>T

Variant summary

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

The NM_012413.4(QPCT):​c.547-1747C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,982 control chromosomes in the GnomAD database, including 25,401 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 0.55 (25401 hom., cov: 31)
• Consequence: QPCT NM_012413.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 25 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QPCT	NM_012413.4	c.547-1747C>T		intron_variant	Intron 3 of 6	ENST00000338415.8	NP_036545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QPCT	ENST00000338415.8	c.547-1747C>T		intron_variant	Intron 3 of 6	1	NM_012413.4	ENSP00000344829.3
QPCT	ENST00000404976.5	c.400-1747C>T		intron_variant	Intron 2 of 5	2		ENSP00000385391.1
QPCT	ENST00000650442.1	c.355-1747C>T		intron_variant	Intron 3 of 3			ENSP00000498156.1
QPCT	ENST00000480050.1	n.457-1747C>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83379 AN: 151862 Hom.: 25351 Cov.: 31

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.549 AC: 83489 AN: 151982 Hom.: 25401 Cov.: 31 AF XY: 0.546 AC XY: 40562 AN XY: 74264

African (AFR) AF: 0.808 AC: 33506 AN: 41480

American (AMR) AF: 0.604 AC: 9226 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3323 AN: 5172

South Asian (SAS) AF: 0.600 AC: 2894 AN: 4820

European-Finnish (FIN) AF: 0.319 AC: 3364 AN: 10540

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27925 AN: 67912

Other (OTH) AF: 0.513 AC: 1081 AN: 2108

Alfa AF: 0.462 Hom.: 56517

Bravo AF: 0.583

Asia WGS AF: 0.608 AC: 2117 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	0.48
DANN	Benign	0.67
PhyloP100		-2.7
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: rs2373000; hg19: chr2-37592628;