2-37368382-A-G

Variant names:

• chr2-37368382-A-G
• rs3770748
• NM_012413.4:c.723+974A>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.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
• Publications: 5 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=-0.89).
• 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 rank	MANE	Protein	UniProt
QPCT	NM_012413.4	c.723+974A>G		intron_variant	Intron 4 of 6	ENST00000338415.8	NP_036545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QPCT	ENST00000338415.8	c.723+974A>G		intron_variant	Intron 4 of 6	1	NM_012413.4	ENSP00000344829.3

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

African (AFR) AF: 0.181 AC: 99 AN: 546

American (AMR) AF: 0.167 AC: 202 AN: 1206

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 82 AN: 898

East Asian (EAS) AF: 0.532 AC: 412 AN: 774

South Asian (SAS) AF: 0.196 AC: 1993 AN: 10160

European-Finnish (FIN) AF: 0.103 AC: 276 AN: 2672

Middle Eastern (MID) AF: 0.0904 AC: 66 AN: 730

European-Non Finnish (NFE) AF: 0.107 AC: 2670 AN: 24944

Other (OTH) AF: 0.131 AC: 291 AN: 2226

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

African (AFR) AF: 0.228 AC: 8262 AN: 36306

American (AMR) AF: 0.244 AC: 2938 AN: 12022

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 321 AN: 3422

East Asian (EAS) AF: 0.539 AC: 2647 AN: 4912

South Asian (SAS) AF: 0.244 AC: 1104 AN: 4532

European-Finnish (FIN) AF: 0.118 AC: 861 AN: 7292

Middle Eastern (MID) AF: 0.193 AC: 44 AN: 228

European-Non Finnish (NFE) AF: 0.127 AC: 8388 AN: 66226

Other (OTH) AF: 0.188 AC: 348 AN: 1850

Alfa AF: 0.141 Hom.: 2735

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
PhyloP100		-0.052
PromoterAI		-0.017	Neutral
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: rs3770748; hg19: chr2-37595525;