Genetic Variant QPCTL:c.886+14C>T (chr19-45698914-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

233 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017659.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPCTL	NM_017659.4	MANE Select	c.886+14C>T		intron	N/A	NP_060129.2
	QPCTL	NM_001163377.2		c.604+14C>T		intron	N/A	NP_001156849.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
QPCTL	ENST00000012049.10	TSL:2 MANE Select	c.886+14C>T	intron	N/A	ENSP00000012049.4
QPCTL	ENST00000366382.8	TSL:2	c.604+14C>T	intron	N/A	ENSP00000387944.2
QPCTL	ENST00000592769.1	TSL:5	n.339+14C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25096

AN:

151594

Hom.:

2223

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.173

AC:

43463

AN:

250616

AF XY:

0.175

show subpopulations

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 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.:

AF XY:

0.182

AC XY:

131947

AN XY:

725416

show subpopulations

African (AFR)

AF:

0.112

AC:

3742

AN:

33368

American (AMR)

AF:

0.0975

AC:

4356

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

7128

AN:

26086

East Asian (EAS)

AF:

0.204

AC:

8092

AN:

39638

South Asian (SAS)

AF:

0.150

AC:

12922

AN:

86166

European-Finnish (FIN)

AF:

0.213

AC:

11330

AN:

53244

Middle Eastern (MID)

AF:

0.185

AC:

1064

AN:

5750

European-Non Finnish (NFE)

AF:

0.186

AC:

205861

AN:

1108396

Other (OTH)

AF:

0.180

AC:

10812

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

11804

23608

35413

47217

59021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7136

14272

21408

28544

35680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.165

AC:

25101

AN:

151704

Hom.:

2220

Cov.:

AF XY:

0.164

AC XY:

12130

AN XY:

74146

show subpopulations

African (AFR)

AF:

0.116

AC:

4787

AN:

41384

American (AMR)

AF:

0.128

AC:

1944

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

982

AN:

3472

East Asian (EAS)

AF:

0.184

AC:

944

AN:

5120

South Asian (SAS)

AF:

0.155

AC:

743

AN:

4806

European-Finnish (FIN)

AF:

0.197

AC:

2072

AN:

10492

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.193

AC:

13079

AN:

67894

Other (OTH)

AF:

0.188

AC:

396

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1043

2087

3130

4174

5217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.186

Hom.:

12027

Bravo

AF:

0.157

Asia WGS

AF:

0.164

AC:

573

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.097

(source)

DANN

Benign

0.45

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over