Genetic Variant CPNE5:c.1563+416T>C (chr6-36743273-A-G) – 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+416T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 979,348 control chromosomes in the GnomAD database, including 134,807 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 0.51 ( 20489 hom., cov: 32)

Exomes 𝑓: 0.52 ( 114318 hom. )

Consequence

CPNE5
NM_020939.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.515

Publications

6 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:

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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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020939.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CPNE5	NM_020939.2	MANE Select	c.1563+416T>C	intron	N/A	NP_065990.1
CPNE5	NM_001376895.1		c.*17T>C	3_prime_UTR	Exon 9 of 9	NP_001363824.1
CPNE5	NM_001376892.1		c.*17T>C	3_prime_UTR	Exon 8 of 8	NP_001363821.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CPNE5	ENST00000244751.7	TSL:1 MANE Select	c.1563+416T>C	intron	N/A	ENSP00000244751.2
CPNE5	ENST00000393189.2	TSL:1	c.687+416T>C	intron	N/A	ENSP00000376885.2
CPNE5	ENST00000493411.2	TSL:1	n.743+416T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77841

AN:

151934

Hom.:

20442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.609

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.440

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.482

GnomAD4 exome

AF:

0.524

AC:

433598

AN:

827294

Hom.:

114318

Cov.:

AF XY:

0.523

AC XY:

199871

AN XY:

382288

show subpopulations

African (AFR)

AF:

0.617

AC:

9660

AN:

15664

American (AMR)

AF:

0.323

AC:

317

AN:

982

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

2509

AN:

5120

East Asian (EAS)

AF:

0.411

AC:

1477

AN:

3598

South Asian (SAS)

AF:

0.437

AC:

7157

AN:

16360

European-Finnish (FIN)

AF:

0.496

AC:

136

AN:

274

Middle Eastern (MID)

AF:

0.477

AC:

768

AN:

1610

European-Non Finnish (NFE)

AF:

0.526

AC:

397959

AN:

756602

Other (OTH)

AF:

0.503

AC:

13615

AN:

27084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

8450

16900

25350

33800

42250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15566

31132

46698

62264

77830

<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:

0.513

AC:

77939

AN:

152054

Hom.:

20489

Cov.:

AF XY:

0.504

AC XY:

37493

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.609

AC:

25261

AN:

41446

American (AMR)

AF:

0.369

AC:

5646

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

1781

AN:

3470

East Asian (EAS)

AF:

0.414

AC:

2143

AN:

5180

South Asian (SAS)

AF:

0.432

AC:

2082

AN:

4818

European-Finnish (FIN)

AF:

0.440

AC:

4657

AN:

10578

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.512

AC:

34773

AN:

67960

Other (OTH)

AF:

0.488

AC:

1029

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1932

3863

5795

7726

9658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.508

Hom.:

77325

Bravo

AF:

0.508

Asia WGS

AF:

0.465

AC:

1618

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.36

(source)

DANN

Benign

0.65

PhyloP100

-0.52

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over