Variant chr7-130308381-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_016352.4(CPA4):c.777G>A(p.Trp259*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00361 in 1,614,060 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 16 hom. )

Consequence

CPA4
NM_016352.4 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 7.14

Variant links:

Genes affected

CPA4 (HGNC:15740): (carboxypeptidase A4) This gene is a member of the carboxypeptidase A/B subfamily, and it is located in a cluster with three other family members on chromosome 7. Carboxypeptidases are zinc-containing exopeptidases that catalyze the release of carboxy-terminal amino acids, and are synthesized as zymogens that are activated by proteolytic cleavage. This gene could be involved in the histone hyperacetylation pathway. It is imprinted and may be a strong candidate gene for prostate cancer aggressiveness. [provided by RefSeq, Jul 2008]

CPA4 links:

CPA4 (HGNC:):

CPA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 7-130308381-G-A is Benign according to our data. Variant chr7-130308381-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 776598.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-130308381-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPA4	NM_016352.4 linkuse as main transcript	c.777G>A	p.Trp259*	stop_gained	8/11	ENST00000222482.10	NP_057436.2	Q9UI42-1A4D1M3
CPA4	NM_001163446.2 linkuse as main transcript	c.678G>A	p.Trp226*	stop_gained	7/10		NP_001156918.1	Q9UI42-2
CPA4	XM_047420438.1 linkuse as main transcript	c.465G>A	p.Trp155*	stop_gained	8/11		XP_047276394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CPA4	ENST00000222482.10 linkuse as main transcript	c.777G>A	p.Trp259*	stop_gained	8/11	1	NM_016352.4	ENSP00000222482.4	Q9UI42-1
CPA4	ENST00000445470.6 linkuse as main transcript	c.678G>A	p.Trp226*	stop_gained	7/10	2		ENSP00000412947.2	Q9UI42-2
CPA4	ENST00000493259.5 linkuse as main transcript	c.465G>A	p.Trp155*	stop_gained	6/9	2		ENSP00000419660.1	B7Z5J4
CPA4	ENST00000488025.1 linkuse as main transcript	n.250G>A		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

377

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00385

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00234

AC:

588

AN:

251442

Hom.:

AF XY:

0.00254

AC XY:

345

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00209

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00349

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00373

AC:

5453

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00365

AC XY:

2652

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00402

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00238

Gnomad4 FIN exome

AF:

0.000861

Gnomad4 NFE exome

AF:

0.00433

Gnomad4 OTH exome

AF:

0.00315

GnomAD4 genome

AF:

0.00248

AC:

377

AN:

152302

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00385

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00376

Hom.:

Bravo

AF:

0.00265

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00235

AC:

285

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00398

EpiControl

AF:

0.00427

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 24, 2017

- -

CPA4-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 19, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.55

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Uncertain

0.81

Vest4

0.27, 0.27, 0.24

GERP RS

5.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over