rs4392869

Variant names:

• chr8-96651036-T-C
• rs4392869
• NM_016134.4:c.-35+5634T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CPQ	NM_016134.4	c.-35+5634T>C		intron_variant	Intron 1 of 7	ENST00000220763.10	NP_057218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPQ	ENST00000220763.10	c.-35+5634T>C		intron_variant	Intron 1 of 7	1	NM_016134.4	ENSP00000220763.5
CPQ	ENST00000517742.1	c.-75+5634T>C		intron_variant	Intron 1 of 3	5		ENSP00000429146.1
CPQ	ENST00000519900.1	c.-140+5634T>C		intron_variant	Intron 1 of 2	4		ENSP00000431024.1

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

African (AFR) AF: 0.474 AC: 19661 AN: 41474

American (AMR) AF: 0.613 AC: 9374 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2570 AN: 3468

East Asian (EAS) AF: 0.525 AC: 2713 AN: 5172

South Asian (SAS) AF: 0.694 AC: 3345 AN: 4818

European-Finnish (FIN) AF: 0.818 AC: 8666 AN: 10598

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53235 AN: 67990

Other (OTH) AF: 0.683 AC: 1442 AN: 2110

Alfa AF: 0.754 Hom.: 22345

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
PhyloP100		2.7
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: rs4392869; hg19: chr8-97663264;