dbSNP rs3213534: CPNE5:c.1563+60C>T (chr6-36743629-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020939.2(CPNE5):c.1563+60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,523,048 control chromosomes in the GnomAD database, including 88,002 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7088 hom., cov: 33)

Exomes 𝑓: 0.34 ( 80914 hom. )

Consequence

CPNE5
NM_020939.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0770

Publications

4 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPNE5	NM_020939.2 link	c.1563+60C>T		intron_variant	Intron 20 of 20	ENST00000244751.7	NP_065990.1	Q9HCH3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE5	ENST00000244751.7 link	c.1563+60C>T		intron_variant	Intron 20 of 20	1	NM_020939.2	ENSP00000244751.2		Q9HCH3-1

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45579

AN:

152136

Hom.:

7088

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.277

GnomAD4 exome

AF:

0.338

AC:

462671

AN:

1370794

Hom.:

80914

AF XY:

0.335

AC XY:

229264

AN XY:

684796

show subpopulations

African (AFR)

AF:

0.244

AC:

7758

AN:

31768

American (AMR)

AF:

0.161

AC:

7125

AN:

44284

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

9066

AN:

25332

East Asian (EAS)

AF:

0.194

AC:

7591

AN:

39138

South Asian (SAS)

AF:

0.237

AC:

19909

AN:

84166

European-Finnish (FIN)

AF:

0.282

AC:

14321

AN:

50762

Middle Eastern (MID)

AF:

0.299

AC:

1629

AN:

5440

European-Non Finnish (NFE)

AF:

0.365

AC:

376991

AN:

1032674

Other (OTH)

AF:

0.319

AC:

18281

AN:

57230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

15097

30194

45290

60387

75484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11564

23128

34692

46256

57820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.299

AC:

45599

AN:

152254

Hom.:

7088

Cov.:

AF XY:

0.292

AC XY:

21710

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.252

AC:

10476

AN:

41542

American (AMR)

AF:

0.223

AC:

3419

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1278

AN:

3472

East Asian (EAS)

AF:

0.206

AC:

1065

AN:

5172

South Asian (SAS)

AF:

0.217

AC:

1049

AN:

4830

European-Finnish (FIN)

AF:

0.269

AC:

2849

AN:

10600

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24526

AN:

68006

Other (OTH)

AF:

0.273

AC:

578

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1686

3372

5058

6744

8430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.324

Hom.:

1282

Bravo

AF:

0.292

Asia WGS

AF:

0.180

AC:

627

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.55

PhyloP100

-0.077

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over