Variant rs3752480 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020939.2(CPNE5):c.1564-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,607,348 control chromosomes in the GnomAD database, including 31,702 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2395 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29307 hom. )

Consequence

CPNE5
NM_020939.2 splice_region, intron

Scores

Splicing: ADA: 0.0003679

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

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:

CPNE5 (HGNC:):

CPNE5 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 (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE5	NM_020939.2 linkuse as main transcript	c.1564-6T>C		splice_region_variant, intron_variant		ENST00000244751.7	NP_065990.1	Q9HCH3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE5	ENST00000244751.7 linkuse as main transcript	c.1564-6T>C		splice_region_variant, intron_variant		1	NM_020939.2	ENSP00000244751.2		Q9HCH3-1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25211

AN:

151938

Hom.:

2398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0643

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.195

AC:

48092

AN:

246112

Hom.:

4956

AF XY:

0.198

AC XY:

26394

AN XY:

133358

show subpopulations

Gnomad AFR exome

AF:

0.0637

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.273

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.197

AC:

286647

AN:

1455292

Hom.:

29307

Cov.:

AF XY:

0.198

AC XY:

143503

AN XY:

723504

show subpopulations

Gnomad4 AFR exome

AF:

0.0597

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.181

Gnomad4 EAS exome

AF:

0.284

Gnomad4 SAS exome

AF:

0.213

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.199

Gnomad4 OTH exome

AF:

0.193

GnomAD4 genome

AF:

0.166

AC:

25195

AN:

152056

Hom.:

2395

Cov.:

AF XY:

0.167

AC XY:

12425

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0641

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.206

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.198

Hom.:

6853

Bravo

AF:

0.162

Asia WGS

AF:

0.194

AC:

676

AN:

3478

EpiCase

AF:

0.211

EpiControl

AF:

0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.3

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00037

dbscSNV1_RF

Benign

0.040

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