Variant 20-35626801-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PVS1_StrongBA1

The NM_001198863.2(CPNE1):c.1237-1A>G variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.0612 in 1,613,150 control chromosomes in the GnomAD database, including 3,430 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.047 ( 261 hom., cov: 31)

Exomes 𝑓: 0.063 ( 3169 hom. )

Consequence

CPNE1
NM_001198863.2 splice_acceptor, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.13

Variant links:

Genes affected

CPNE1 (HGNC:2314): (copine 1) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene encodes a calcium-dependent protein that also contains two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. However, the encoded protein does not contain a predicted signal sequence or transmembrane domains. This protein has a broad tissue distribution and it may function in membrane trafficking. This gene and the gene for RNA binding motif protein 12 overlap at map location 20q11.21. Alternate splicing results in multiple transcript variants encoding different proteins. [provided by RefSeq, Aug 2008]

CPNE1 links:

CPNE1 (HGNC:):

CPNE1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.14463067 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.2, offset of 0 (no position change), new splice context is: aatgggcttgtccccagcAGtac. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE1	NM_152925.3 linkuse as main transcript	c.1239A>G	p.Gln413Gln	splice_region_variant, synonymous_variant	15/16	ENST00000397443.7	NP_690902.1	Q99829

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE1	ENST00000397443.7 linkuse as main transcript	c.1239A>G	p.Gln413Gln	splice_region_variant, synonymous_variant	15/16	5	NM_152925.3	ENSP00000380585.1		Q99829
CPNE1	ENST00000437340.5 linkuse as main transcript	c.1237-1A>G		splice_acceptor_variant, intron_variant		1		ENSP00000415597.1		F2Z2V0

Frequencies

GnomAD3 genomes

AF:

0.0471

AC:

7170

AN:

152106

Hom.:

260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.0703

Gnomad ASJ

AF:

0.0611

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0396

Gnomad FIN

AF:

0.0402

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0675

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0616

AC:

15439

AN:

250822

Hom.:

687

AF XY:

0.0596

AC XY:

8083

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.00929

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.0530

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0456

Gnomad FIN exome

AF:

0.0456

Gnomad NFE exome

AF:

0.0666

Gnomad OTH exome

AF:

0.0592

GnomAD4 exome

AF:

0.0626

AC:

91508

AN:

1460926

Hom.:

3169

Cov.:

AF XY:

0.0621

AC XY:

45131

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.00900

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.0548

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0482

Gnomad4 FIN exome

AF:

0.0464

Gnomad4 NFE exome

AF:

0.0668

Gnomad4 OTH exome

AF:

0.0563

GnomAD4 genome

AF:

0.0472

AC:

7178

AN:

152224

Hom.:

261

Cov.:

AF XY:

0.0457

AC XY:

3399

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.0707

Gnomad4 ASJ

AF:

0.0611

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0398

Gnomad4 FIN

AF:

0.0402

Gnomad4 NFE

AF:

0.0675

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0618

Hom.:

574

Bravo

AF:

0.0485

TwinsUK

AF:

0.0666

AC:

247

ALSPAC

AF:

0.0651

AC:

251

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.0733

AC:

630

ExAC

AF:

0.0592

AC:

7182

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0668

EpiControl

AF:

0.0640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.93

ClinPred

0.025

GERP RS

4.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.98

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.98

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over