Genetic Variant QPCTL:n.-206A>C (chr19-45692498-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000677024.1(QPCTL):n.-206A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 463,776 control chromosomes in the GnomAD database, including 380 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 0.028 ( 100 hom., cov: 33)

Exomes 𝑓: 0.036 ( 280 hom. )

Consequence

QPCTL
ENST00000677024.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.934

Publications

15 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:

SNRPD2 (HGNC:11159): (small nuclear ribonucleoprotein D2 polypeptide) The protein encoded by this gene belongs to the small nuclear ribonucleoprotein core protein family. It is required for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

SNRPD2 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=-0.88).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0281 (4286/152354) while in subpopulation NFE AF = 0.0456 (3102/68036). AF 95% confidence interval is 0.0443. There are 100 homozygotes in GnomAd4. There are 2058 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QPCTL	NM_017659.4 link	c.-206A>C		upstream_gene_variant		ENST00000012049.10	NP_060129.2	Q9NXS2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QPCTL	ENST00000012049.10 link	c.-206A>C		upstream_gene_variant		2	NM_017659.4	ENSP00000012049.4		Q9NXS2-1

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4287

AN:

152236

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00825

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0107

Gnomad FIN

AF:

0.0468

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0456

Gnomad OTH

AF:

0.0177

GnomAD4 exome

AF:

0.0356

AC:

11081

AN:

311422

Hom.:

280

Cov.:

AF XY:

0.0344

AC XY:

5507

AN XY:

160088

show subpopulations

African (AFR)

AF:

0.00868

AC:

AN:

8988

American (AMR)

AF:

0.0108

AC:

116

AN:

10764

Ashkenazi Jewish (ASJ)

AF:

0.0105

AC:

106

AN:

10114

East Asian (EAS)

AF:

0.0000401

AC:

AN:

24922

South Asian (SAS)

AF:

0.0109

AC:

155

AN:

14260

European-Finnish (FIN)

AF:

0.0396

AC:

888

AN:

22408

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

1470

European-Non Finnish (NFE)

AF:

0.0456

AC:

9110

AN:

199594

Other (OTH)

AF:

0.0326

AC:

617

AN:

18902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

530

1060

1589

2119

2649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.0281

AC:

4286

AN:

152354

Hom.:

100

Cov.:

AF XY:

0.0276

AC XY:

2058

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00822

AC:

342

AN:

41590

American (AMR)

AF:

0.0137

AC:

209

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0108

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0468

AC:

497

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0456

AC:

3102

AN:

68036

Other (OTH)

AF:

0.0175

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

221

443

664

886

1107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0383

Hom.:

360

Bravo

AF:

0.0252

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.9

(source)

DANN

Benign

0.67

PhyloP100

-0.93

PromoterAI

0.040

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over