rs632899

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_133459.4(CCBE1):c.266-30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,612,994 control chromosomes in the GnomAD database, including 168,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15425 hom., cov: 33)

Exomes 𝑓: 0.46 ( 152771 hom. )

Consequence

CCBE1
NM_133459.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.251

Publications

9 publications found

Variant links:

Genes affected

CCBE1 (HGNC:29426): (collagen and calcium binding EGF domains 1) This gene is thought to function in extracellular matrix remodeling and migration. It is predominantly expressed in the ovary, but down regulated in ovarian cancer cell lines and primary carcinomas, suggesting its role as a tumour suppressor. Mutations in this gene have been associated with Hennekam lymphangiectasia-lymphedema syndrome, a generalized lymphatic dysplasia in humans. [provided by RefSeq, Mar 2010]

CCBE1 Gene-Disease associations (from GenCC):

Hennekam lymphangiectasia-lymphedema syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Hennekam syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CCBE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 18-59469637-A-G is Benign according to our data. Variant chr18-59469637-A-G is described in ClinVar as Benign. ClinVar VariationId is 262352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCBE1	NM_133459.4 link	c.266-30T>C		intron_variant	Intron 3 of 10	ENST00000439986.9	NP_597716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCBE1	ENST00000439986.9 link	c.266-30T>C		intron_variant	Intron 3 of 10	1	NM_133459.4	ENSP00000404464.2

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68395

AN:

151980

Hom.:

15397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.444

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.507

Gnomad FIN

AF:

0.482

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.437

GnomAD2 exomes

AF:

0.446

AC:

111838

AN:

250758

AF XY:

0.454

show subpopulations

Gnomad AFR exome

AF:

0.440

Gnomad AMR exome

AF:

0.322

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.472

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.453

GnomAD4 exome

AF:

0.456

AC:

665714

AN:

1460896

Hom.:

152771

Cov.:

AF XY:

0.459

AC XY:

333440

AN XY:

726748

show subpopulations

African (AFR)

AF:

0.443

AC:

14828

AN:

33458

American (AMR)

AF:

0.325

AC:

14528

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

12970

AN:

26132

East Asian (EAS)

AF:

0.417

AC:

16557

AN:

39694

South Asian (SAS)

AF:

0.514

AC:

44358

AN:

86232

European-Finnish (FIN)

AF:

0.474

AC:

25205

AN:

53220

Middle Eastern (MID)

AF:

0.501

AC:

2716

AN:

5424

European-Non Finnish (NFE)

AF:

0.456

AC:

506755

AN:

1111668

Other (OTH)

AF:

0.461

AC:

27797

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

20951

41903

62854

83806

104757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15120

30240

45360

60480

75600

<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:

0.450

AC:

68472

AN:

152098

Hom.:

15425

Cov.:

AF XY:

0.452

AC XY:

33628

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.444

AC:

18416

AN:

41474

American (AMR)

AF:

0.389

AC:

5947

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

1764

AN:

3472

East Asian (EAS)

AF:

0.432

AC:

2235

AN:

5168

South Asian (SAS)

AF:

0.509

AC:

2452

AN:

4818

European-Finnish (FIN)

AF:

0.482

AC:

5098

AN:

10574

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.459

AC:

31236

AN:

67994

Other (OTH)

AF:

0.444

AC:

936

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1983

3966

5948

7931

9914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.454

Hom.:

7711

Bravo

AF:

0.437

Asia WGS

AF:

0.467

AC:

1626

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 60% of patients studied by a panel of primary immunodeficiencies. Number of patients: 57. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hennekam lymphangiectasia-lymphedema syndrome 1

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.091

(source)

DANN

Benign

0.24

PhyloP100

-0.25

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over