NM_012413.4:c.121-3796A>G

Variant names:

• chr2-37348993-A-G
• rs3770752
• NM_012413.4:c.121-3796A>G

Variant summary

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

The NM_012413.4(QPCT):​c.121-3796A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,088 control chromosomes in the GnomAD database, including 6,469 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 0.26 (6469 hom., cov: 32)
• Consequence: QPCT NM_012413.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 9 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QPCT	NM_012413.4	c.121-3796A>G		intron_variant	Intron 1 of 6	ENST00000338415.8	NP_036545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QPCT	ENST00000338415.8	c.121-3796A>G		intron_variant	Intron 1 of 6	1	NM_012413.4	ENSP00000344829.3
QPCT	ENST00000404976.5	c.120+4142A>G		intron_variant	Intron 1 of 5	2		ENSP00000385391.1
QPCT	ENST00000650442.1	c.-72-3796A>G		intron_variant	Intron 1 of 3			ENSP00000498156.1
QPCT	ENST00000470075.1	n.125-3796A>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39541 AN: 151970 Hom.: 6475 Cov.: 32

Gnomad AFR AF: 0.0769

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.260 AC: 39537 AN: 152088 Hom.: 6469 Cov.: 32 AF XY: 0.262 AC XY: 19479 AN XY: 74322

African (AFR) AF: 0.0767 AC: 3184 AN: 41506

American (AMR) AF: 0.266 AC: 4068 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1430 AN: 3470

East Asian (EAS) AF: 0.133 AC: 688 AN: 5180

South Asian (SAS) AF: 0.166 AC: 803 AN: 4824

European-Finnish (FIN) AF: 0.438 AC: 4624 AN: 10558

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23672 AN: 67964

Other (OTH) AF: 0.290 AC: 613 AN: 2112

Alfa AF: 0.296 Hom.: 4262

Bravo AF: 0.242

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.72
PhyloP100		-1.0
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: rs3770752; hg19: chr2-37576136;