Variant 7-130310900-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016352.4(CPA4):c.907G>T(p.Gly303Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,613,408 control chromosomes in the GnomAD database, including 110,736 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.33 ( 8671 hom., cov: 32)

Exomes 𝑓: 0.37 ( 102065 hom. )

Consequence

CPA4
NM_016352.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0180

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008575439).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CPA4	NM_016352.4 linkuse as main transcript	c.907G>T	p.Gly303Cys	missense_variant	9/11	ENST00000222482.10	NP_057436.2
CPA4	NM_001163446.2 linkuse as main transcript	c.808G>T	p.Gly270Cys	missense_variant	8/10		NP_001156918.1
CPA4	XM_047420438.1 linkuse as main transcript	c.595G>T	p.Gly199Cys	missense_variant	9/11		XP_047276394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPA4	ENST00000222482.10 linkuse as main transcript	c.907G>T	p.Gly303Cys	missense_variant	9/11	1	NM_016352.4	ENSP00000222482	P1	Q9UI42-1
CPA4	ENST00000445470.6 linkuse as main transcript	c.808G>T	p.Gly270Cys	missense_variant	8/10	2		ENSP00000412947		Q9UI42-2
CPA4	ENST00000493259.5 linkuse as main transcript	c.595G>T	p.Gly199Cys	missense_variant	7/9	2		ENSP00000419660
CPA4	ENST00000488025.1 linkuse as main transcript	n.380G>T		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50351

AN:

151896

Hom.:

8672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.406

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.357

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.339

GnomAD3 exomes

AF:

0.349

AC:

87711

AN:

251456

Hom.:

15768

AF XY:

0.356

AC XY:

48340

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.346

Gnomad EAS exome

AF:

0.364

Gnomad SAS exome

AF:

0.376

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.350

GnomAD4 exome

AF:

0.372

AC:

543491

AN:

1461394

Hom.:

102065

Cov.:

AF XY:

0.372

AC XY:

270456

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.267

Gnomad4 ASJ exome

AF:

0.352

Gnomad4 EAS exome

AF:

0.349

Gnomad4 SAS exome

AF:

0.371

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.358

GnomAD4 genome

AF:

0.331

AC:

50366

AN:

152014

Hom.:

8671

Cov.:

AF XY:

0.332

AC XY:

24651

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.302

Gnomad4 ASJ

AF:

0.337

Gnomad4 EAS

AF:

0.361

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.357

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.375

Hom.:

27083

Bravo

AF:

0.322

TwinsUK

AF:

0.389

AC:

1442

ALSPAC

AF:

0.384

AC:

1481

ESP6500AA

AF:

0.228

AC:

1003

ESP6500EA

AF:

0.385

AC:

3310

ExAC

AF:

0.348

AC:

42227

Asia WGS

AF:

0.388

AC:

1350

AN:

3478

EpiCase

AF:

0.390

EpiControl

AF:

0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.032

T;.;T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.42

.;T;T;T

MetaRNN

Benign

0.0086

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.060

N;.;.;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

0.92

.;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.082

.;T;T;T

Sift4G

Benign

0.084

.;T;T;T

Polyphen

0.0040

B;.;.;B

Vest4

0.16, 0.085, 0.13

MPC

0.12

ClinPred

0.0069

GERP RS

0.48

Varity_R

0.43

gMVP

0.59

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over