Variant 7-28995812-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_031311.5(CPVL):c.1391G>A(p.Arg464Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,606,928 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 20 hom. )

Consequence

CPVL
NM_031311.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.33

Variant links:

Genes affected

CPVL (HGNC:14399): (carboxypeptidase vitellogenic like) The protein encoded by this gene is a carboxypeptidase and bears strong sequence similarity to serine carboxypeptidases. Carboxypeptidases are a large class of proteases that act to cleave a single amino acid from the carboxy termini of proteins or peptides. The exact function of this protein, however, has not been determined. [provided by RefSeq, Jan 2017]

CPVL links:

CPVL-AS2 (HGNC:56138): (CPVL antisense RNA 2)

CPVL-AS2 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=0.019909263).

BP6

Variant 7-28995812-C-T is Benign according to our data. Variant chr7-28995812-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 733777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPVL	NM_031311.5 linkuse as main transcript	c.1391G>A	p.Arg464Gln	missense_variant	13/13	ENST00000265394.10
CPVL-AS2	NR_038965.1 linkuse as main transcript	n.133-353C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPVL	ENST00000265394.10 linkuse as main transcript	c.1391G>A	p.Arg464Gln	missense_variant	13/13	1	NM_031311.5	P1
CPVL-AS2	ENST00000609389.5 linkuse as main transcript	n.133-353C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

409

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00237

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00459

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00288

AC:

706

AN:

245150

Hom.:

AF XY:

0.00301

AC XY:

399

AN XY:

132560

show subpopulations

Gnomad AFR exome

AF:

0.000626

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.000300

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.00232

Gnomad NFE exome

AF:

0.00498

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.00430

AC:

6251

AN:

1454752

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

3110

AN XY:

723646

show subpopulations

Gnomad4 AFR exome

AF:

0.000665

Gnomad4 AMR exome

AF:

0.00126

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.00131

Gnomad4 FIN exome

AF:

0.00214

Gnomad4 NFE exome

AF:

0.00523

Gnomad4 OTH exome

AF:

0.00238

GnomAD4 genome

AF:

0.00269

AC:

409

AN:

152176

Hom.:

Cov.:

AF XY:

0.00237

AC XY:

176

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00237

Gnomad4 NFE

AF:

0.00459

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00407

Hom.:

Bravo

AF:

0.00245

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00309

AC:

375

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00422

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

T;T;.;T

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

.;.;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.020

T;T;T;T

MetaSVM

Uncertain

0.78

MutationAssessor

Pathogenic

3.1

M;M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Uncertain

0.012

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.42

MVP

0.98

MPC

0.37

ClinPred

0.059

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.65

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