rs11083779

Variant names:

• chr19-45701620-T-C
• rs11083779
• NM_017659.4:c.887-178T>C

Variant summary

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

The NM_017659.4(QPCTL):​c.887-178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 152,242 control chromosomes in the GnomAD database, including 382 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 0.062 (382 hom., cov: 31)
• Consequence: QPCTL NM_017659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805
• Publications: 8 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPCTL	NM_017659.4	MANE Select	c.887-178T>C		intron	N/A	NP_060129.2
	QPCTL	NM_001163377.2		c.605-178T>C		intron	N/A	NP_001156849.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPCTL	ENST00000012049.10	TSL:2 MANE Select	c.887-178T>C		intron	N/A	ENSP00000012049.4
	QPCTL	ENST00000366382.8	TSL:2	c.605-178T>C		intron	N/A	ENSP00000387944.2
	QPCTL	ENST00000592769.1	TSL:5	n.340-178T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9370 AN: 152124 Hom.: 380 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0757

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.0535

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

GnomAD4 genome AF: 0.0616 AC: 9378 AN: 152242 Hom.: 382 Cov.: 31 AF XY: 0.0600 AC XY: 4465 AN XY: 74454

African (AFR) AF: 0.108 AC: 4491 AN: 41540

American (AMR) AF: 0.0314 AC: 479 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0758 AC: 366 AN: 4830

European-Finnish (FIN) AF: 0.0363 AC: 385 AN: 10618

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3212 AN: 68004

Other (OTH) AF: 0.0530 AC: 112 AN: 2114

Alfa AF: 0.0686 Hom.: 222

Bravo AF: 0.0609

Asia WGS AF: 0.0260 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.67
PhyloP100		-0.81
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: rs11083779; hg19: chr19-46204878;