Variant rs632899 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

CCBE1 (HGNC:):

CCBE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
CCBE1	NM_133459.4 linkuse as main transcript	c.266-30T>C		intron_variant		ENST00000439986.9	NP_597716.1	Q6UXH8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCBE1	ENST00000439986.9 linkuse as main transcript	c.266-30T>C		intron_variant		1	NM_133459.4	ENSP00000404464.2		Q6UXH8-1

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

GnomAD3 exomes

AF:

0.446

AC:

111838

AN:

250758

Hom.:

25575

AF XY:

0.454

AC XY:

61599

AN XY:

135542

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 SAS exome

AF:

0.517

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

Gnomad4 AFR exome

AF:

0.443

Gnomad4 AMR exome

AF:

0.325

Gnomad4 ASJ exome

AF:

0.496

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.514

Gnomad4 FIN exome

AF:

0.474

Gnomad4 NFE exome

AF:

0.456

Gnomad4 OTH exome

AF:

0.461

GnomAD4 genome

AF:

0.450

AC:

68472

AN:

152098

Hom.:

15425

Cov.:

AF XY:

0.452

AC XY:

33628

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.444

Gnomad4 AMR

AF:

0.389

Gnomad4 ASJ

AF:

0.508

Gnomad4 EAS

AF:

0.432

Gnomad4 SAS

AF:

0.509

Gnomad4 FIN

AF:

0.482

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.453

Hom.:

5427

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

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Hennekam lymphangiectasia-lymphedema syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.091

DANN

Benign

0.24

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