Variant 6-36745147-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_020939.2(CPNE5):c.1332T>G(p.Asn444Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,612,894 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 9 hom. )

Consequence

CPNE5
NM_020939.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.33

Variant links:

Genes affected

CPNE5 (HGNC:2318): (copine 5) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a calcium-dependent protein containing two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. More variants may exist, but their full-length natures could not be determined. [provided by RefSeq, Sep 2015]

CPNE5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 6-36745147-A-C is Benign according to our data. Variant chr6-36745147-A-C is described in ClinVar as [Benign]. Clinvar id is 791398.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000508 (742/1460576) while in subpopulation AMR AF= 0.0164 (735/44710). AF 95% confidence interval is 0.0155. There are 9 homozygotes in gnomad4_exome. There are 324 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE5	NM_020939.2 linkuse as main transcript	c.1332T>G	p.Asn444Lys	missense_variant	18/21	ENST00000244751.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE5	ENST00000244751.7 linkuse as main transcript	c.1332T>G	p.Asn444Lys	missense_variant	18/21	1	NM_020939.2	A1	Q9HCH3-1

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00268

AC:

672

AN:

250830

Hom.:

AF XY:

0.00212

AC XY:

287

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0193

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000508

AC:

742

AN:

1460576

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

324

AN XY:

726658

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0164

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000532

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.0000541

Hom.:

Bravo

AF:

0.00152

ExAC

AF:

0.00232

AC:

282

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.9

DANN

Benign

0.91

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0072

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

0.50

N;N;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.47

N;N

REVEL

Benign

0.084

Sift

Benign

0.32

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.0

.;B

Vest4

0.39

MutPred

0.68

.;Gain of ubiquitination at N444 (P = 0.03);

MVP

0.24

MPC

0.82

ClinPred

0.041

GERP RS

-9.8

Varity_R

0.054

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.79

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.79

Position offset: -1

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