Genetic Variant CCBE1:c.265+28G>C (chr18-59480158-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_133459.4(CCBE1):c.265+28G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 1,389,622 control chromosomes in the GnomAD database, including 266,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33110 hom., cov: 34)

Exomes 𝑓: 0.61 ( 233413 hom. )

Consequence

CCBE1
NM_133459.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.968

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 18-59480158-C-G is Benign according to our data. Variant chr18-59480158-C-G is described in ClinVar as [Benign]. Clinvar id is 262351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCBE1	NM_133459.4 link	c.265+28G>C		intron_variant	Intron 3 of 10	ENST00000439986.9	NP_597716.1	Q6UXH8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCBE1	ENST00000439986.9 link	c.265+28G>C		intron_variant	Intron 3 of 10	1	NM_133459.4	ENSP00000404464.2		Q6UXH8-1

Frequencies

GnomAD3 genomes

AF:

0.657

AC:

99782

AN:

151942

Hom.:

33095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.728

Gnomad AMI

AF:

0.769

Gnomad AMR

AF:

0.691

Gnomad ASJ

AF:

0.550

Gnomad EAS

AF:

0.844

Gnomad SAS

AF:

0.604

Gnomad FIN

AF:

0.586

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.610

Gnomad OTH

AF:

0.670

GnomAD3 exomes

AF:

0.645

AC:

158385

AN:

245694

Hom.:

52008

AF XY:

0.635

AC XY:

84439

AN XY:

132898

show subpopulations

Gnomad AFR exome

AF:

0.729

Gnomad AMR exome

AF:

0.734

Gnomad ASJ exome

AF:

0.569

Gnomad EAS exome

AF:

0.842

Gnomad SAS exome

AF:

0.589

Gnomad FIN exome

AF:

0.591

Gnomad NFE exome

AF:

0.606

Gnomad OTH exome

AF:

0.623

GnomAD4 exome

AF:

0.611

AC:

755824

AN:

1237562

Hom.:

233413

Cov.:

AF XY:

0.609

AC XY:

382182

AN XY:

627208

show subpopulations

Gnomad4 AFR exome

AF:

0.719

Gnomad4 AMR exome

AF:

0.733

Gnomad4 ASJ exome

AF:

0.561

Gnomad4 EAS exome

AF:

0.831

Gnomad4 SAS exome

AF:

0.587

Gnomad4 FIN exome

AF:

0.593

Gnomad4 NFE exome

AF:

0.596

Gnomad4 OTH exome

AF:

0.621

GnomAD4 genome

AF:

0.657

AC:

99840

AN:

152060

Hom.:

33110

Cov.:

AF XY:

0.655

AC XY:

48698

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.728

Gnomad4 AMR

AF:

0.691

Gnomad4 ASJ

AF:

0.550

Gnomad4 EAS

AF:

0.844

Gnomad4 SAS

AF:

0.602

Gnomad4 FIN

AF:

0.586

Gnomad4 NFE

AF:

0.610

Gnomad4 OTH

AF:

0.662

Alfa

AF:

0.617

Hom.:

5269

Bravo

AF:

0.674

Asia WGS

AF:

0.708

AC:

2458

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 82. Only high quality variants are reported. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.43

DANN

Benign

0.45

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over