rs4392869

Positions:

• chr8-96651036-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016134.4(CPQ):​c.-35+5634T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,118 control chromosomes in the GnomAD database, including 35,667 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 0.67 (35667 hom., cov: 33)
• Consequence: CPQ NM_016134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67

Genes affected

CPQ (HGNC:16910): (carboxypeptidase Q) This gene encodes a metallopeptidase that belongs to the peptidase M28 family. The encoded protein may catalyze the cleavage of dipeptides with unsubstituted terminals into amino acids. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPQ	NM_016134.4	c.-35+5634T>C		intron_variant		ENST00000220763.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPQ	ENST00000220763.10	c.-35+5634T>C		intron_variant		1	NM_016134.4	P1
CPQ	ENST00000517742.1	c.-75+5634T>C		intron_variant		5
CPQ	ENST00000519900.1	c.-140+5634T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101839 AN: 151998 Hom.: 35655 Cov.: 33

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.670 AC: 101894 AN: 152118 Hom.: 35667 Cov.: 33 AF XY: 0.670 AC XY: 49843 AN XY: 74384

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.683

Alfa AF: 0.754 Hom.: 19896

Bravo AF: 0.647

Asia WGS AF: 0.613 AC: 2131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.87

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: rs4392869; hg19: chr8-97663264;