Genetic Variant CPQ:p.Met1fs (chr8-96784889-G-GA) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_016134.4(CPQ):c.1dupA(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,566,230 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

CPQ
NM_016134.4 frameshift, start_lost

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.56

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:

LOC124901985 (HGNC:):

LOC124901985 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 8-96784889-G-GA is Benign according to our data. Variant chr8-96784889-G-GA is described in ClinVar as Likely_benign. ClinVar VariationId is 422436.Status of the report is criteria_provided_single_submitter, 1 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.1dupA	p.Met1fs	frameshift start_lost	Exon 2 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.1dupA	p.Met1fs	frameshift start_lost	Exon 2 of 8	ENSP00000220763.5	Q9Y646
CPQ	ENST00000960277.1		c.1dupA	p.Met1fs	frameshift start_lost	Exon 2 of 9	ENSP00000630336.1
CPQ	ENST00000863818.1		c.1dupA	p.Met1fs	frameshift start_lost	Exon 2 of 9	ENSP00000533877.1

Frequencies

GnomAD3 genomes

AF:

0.00233

AC:

348

AN:

149246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000335

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000100

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000119

Gnomad OTH

AF:

0.000488

GnomAD2 exomes

AF:

0.000989

AC:

200

AN:

202310

AF XY:

0.000786

show subpopulations

Gnomad AFR exome

AF:

0.00920

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.000755

Gnomad EAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.000264

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.000437

GnomAD4 exome

AF:

0.000320

AC:

454

AN:

1416876

Hom.:

Cov.:

AF XY:

0.000274

AC XY:

193

AN XY:

704154

show subpopulations

African (AFR)

AF:

0.00817

AC:

254

AN:

31084

American (AMR)

AF:

0.000613

AC:

AN:

37544

Ashkenazi Jewish (ASJ)

AF:

0.000207

AC:

AN:

24168

East Asian (EAS)

AF:

0.0000768

AC:

AN:

39062

South Asian (SAS)

AF:

0.000294

AC:

AN:

81516

European-Finnish (FIN)

AF:

0.000115

AC:

AN:

52098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5504

European-Non Finnish (NFE)

AF:

0.000104

AC:

113

AN:

1087622

Other (OTH)

AF:

0.000446

AC:

AN:

58278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.401

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00233

AC:

348

AN:

149354

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

169

AN XY:

72812

show subpopulations

African (AFR)

AF:

0.00817

AC:

333

AN:

40742

American (AMR)

AF:

0.000334

AC:

AN:

14952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4662

European-Finnish (FIN)

AF:

0.000100

AC:

AN:

9988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000119

AC:

AN:

67172

Other (OTH)

AF:

0.000483

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00109

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Mutation Taster

=300/0

polymorphism

(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

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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