Genetic Variant CPQ:p.Leu151Pro (chr8-96834991-T-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016134.4(CPQ):c.452T>C(p.Leu151Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000529 in 1,613,202 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 4 hom. )

Consequence

CPQ
NM_016134.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.30

Publications

0 publications found

Variant links:

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]

CPQ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011528283).

BP6

Variant 8-96834991-T-C is Benign according to our data. Variant chr8-96834991-T-C is described in ClinVar as Benign. ClinVar VariationId is 712028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016134.4. 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
	CPQ	NM_016134.4	MANE Select	c.452T>C	p.Leu151Pro	missense	Exon 3 of 8	NP_057218.1	Q9Y646

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPQ	ENST00000220763.10	TSL:1 MANE Select	c.452T>C	p.Leu151Pro	missense	Exon 3 of 8	ENSP00000220763.5	Q9Y646
CPQ	ENST00000960277.1		c.452T>C	p.Leu151Pro	missense	Exon 3 of 9	ENSP00000630336.1
CPQ	ENST00000863818.1		c.452T>C	p.Leu151Pro	missense	Exon 3 of 9	ENSP00000533877.1

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

434

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000785

AC:

196

AN:

249812

AF XY:

0.000533

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.000497

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000288

AC:

421

AN:

1460874

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

188

AN XY:

726774

show subpopulations

African (AFR)

AF:

0.0107

AC:

356

AN:

33408

American (AMR)

AF:

0.000674

AC:

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111606

Other (OTH)

AF:

0.000431

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00284

AC:

433

AN:

152328

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00998

AC:

415

AN:

41578

American (AMR)

AF:

0.000720

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68038

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000908

Hom.:

Bravo

AF:

0.00304

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000997

AC:

121

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.51

MutationAssessor

Pathogenic

3.2

PhyloP100

7.3

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.52

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.025

Polyphen

0.99

Vest4

0.94

MVP

0.68

MPC

0.57

ClinPred

0.041

GERP RS

5.7

Varity_R

0.94

gMVP

0.97

Mutation Taster

=50/50

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over