Genetic Variant CPNE7:c.1062-54T>C (chr16-89589843-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_153636.3(CPNE7):c.1062-54T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,598,050 control chromosomes in the GnomAD database, including 237,167 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 0.52 ( 21134 hom., cov: 32)

Exomes 𝑓: 0.54 ( 216033 hom. )

Consequence

CPNE7
NM_153636.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

24 publications found

Variant links:

Genes affected

CPNE7 (HGNC:2320): (copine 7) This gene encodes a member of the copine family, which is composed of calcium-dependent membrane-binding proteins. The gene product contains two N-terminal C2 domains and one von Willebrand factor A domain. The encoded protein may be involved in membrane trafficking. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

CPNE7 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=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153636.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE7	NM_153636.3	MANE Select	c.1062-54T>C		intron	N/A	NP_705900.1	Q9UBL6-2
	CPNE7	NM_014427.5		c.1287-54T>C		intron	N/A	NP_055242.1	Q9UBL6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CPNE7	ENST00000319518.13	TSL:1 MANE Select	c.1062-54T>C	intron	N/A	ENSP00000317374.8	Q9UBL6-2
CPNE7	ENST00000268720.9	TSL:1	c.1287-54T>C	intron	N/A	ENSP00000268720.5	Q9UBL6-1
CPNE7	ENST00000936168.1		c.1110-54T>C	intron	N/A	ENSP00000606227.1

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

79656

AN:

151960

Hom.:

21102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.520

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.697

Gnomad SAS

AF:

0.687

Gnomad FIN

AF:

0.560

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.515

Gnomad OTH

AF:

0.474

GnomAD4 exome

AF:

0.544

AC:

787311

AN:

1445972

Hom.:

216033

AF XY:

0.547

AC XY:

393395

AN XY:

719774

show subpopulations

African (AFR)

AF:

0.503

AC:

16687

AN:

33164

American (AMR)

AF:

0.596

AC:

26252

AN:

44066

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

13221

AN:

25940

East Asian (EAS)

AF:

0.627

AC:

24787

AN:

39548

South Asian (SAS)

AF:

0.658

AC:

56279

AN:

85530

European-Finnish (FIN)

AF:

0.549

AC:

28725

AN:

52316

Middle Eastern (MID)

AF:

0.410

AC:

2349

AN:

5728

European-Non Finnish (NFE)

AF:

0.534

AC:

586975

AN:

1099790

Other (OTH)

AF:

0.535

AC:

32036

AN:

59890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

17750

35499

53249

70998

88748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16978

33956

50934

67912

84890

<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:

0.524

AC:

79741

AN:

152078

Hom.:

21134

Cov.:

AF XY:

0.528

AC XY:

39278

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.499

AC:

20714

AN:

41502

American (AMR)

AF:

0.520

AC:

7954

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1795

AN:

3468

East Asian (EAS)

AF:

0.697

AC:

3607

AN:

5176

South Asian (SAS)

AF:

0.688

AC:

3318

AN:

4826

European-Finnish (FIN)

AF:

0.560

AC:

5912

AN:

10564

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.515

AC:

34966

AN:

67944

Other (OTH)

AF:

0.479

AC:

1012

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2025

4050

6074

8099

10124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.518

Hom.:

65847

Bravo

AF:

0.518

Asia WGS

AF:

0.687

AC:

2387

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.029

(source)

DANN

Benign

0.27

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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