rs11083779

chr19-45701620-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
QPCTL	NM_017659.4	c.887-178T>C		intron_variant		ENST00000012049.10
QPCTL	NM_001163377.2	c.605-178T>C		intron_variant
QPCTL	XM_047438997.1	c.787-178T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QPCTL	ENST00000012049.10	c.887-178T>C		intron_variant		2	NM_017659.4	P1

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

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0314

Gnomad4 ASJ AF: 0.0893

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0758

Gnomad4 FIN AF: 0.0363

Gnomad4 NFE AF: 0.0472

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0627 Hom.: 89

Bravo AF: 0.0609

Asia WGS AF: 0.0260 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.59
Dann	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs11083779; hg19: chr19-46204878;