Variant 3-148883682-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001870.4(CPA3):c.848C>T(p.Thr283Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00589 in 1,614,030 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 36 hom. )

Consequence

CPA3
NM_001870.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.05

Variant links:

Genes affected

CPA3 (HGNC:2298): (carboxypeptidase A3) This gene encodes a member of the carboxypeptidase A family of zinc metalloproteases. The encoded preproprotein is proteolytically processed to generate a mature protease that is released by mast cells and may be involved in the degradation of endogenous proteins and the inactivation of venom-associated peptides. Expression of this gene may be elevated in human asthma patients. [provided by RefSeq, Nov 2015]

CPA3 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012537181).

BP6

Variant 3-148883682-C-T is Benign according to our data. Variant chr3-148883682-C-T is described in ClinVar as [Benign]. Clinvar id is 770894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPA3	NM_001870.4 linkuse as main transcript	c.848C>T	p.Thr283Met	missense_variant	9/11	ENST00000296046.4	NP_001861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CPA3	ENST00000296046.4 linkuse as main transcript	c.848C>T	p.Thr283Met	missense_variant	9/11	1	NM_001870.4	ENSP00000296046	P1
	ENST00000488190.1 linkuse as main transcript	n.163-13593G>A		intron_variant, non_coding_transcript_variant		1
CPA3	ENST00000477926.1 linkuse as main transcript	n.325C>T		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.00474

AC:

721

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00687

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00457

AC:

1147

AN:

251102

Hom.:

AF XY:

0.00442

AC XY:

599

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.00706

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00601

AC:

8778

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

4249

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.00695

Gnomad4 OTH exome

AF:

0.00538

GnomAD4 genome

AF:

0.00474

AC:

721

AN:

152250

Hom.:

Cov.:

AF XY:

0.00488

AC XY:

363

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.00687

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00568

Hom.:

Bravo

AF:

0.00386

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00709

AC:

ExAC

AF:

0.00500

AC:

607

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00513

EpiControl

AF:

0.00581

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.26

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.66

MVP

0.52

MPC

0.17

ClinPred

0.029

GERP RS

4.8

Varity_R

0.44

gMVP

0.70

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over