Variant rs1663549 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.265+26C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,413,438 control chromosomes in the GnomAD database, including 53,500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6018 hom., cov: 33)

Exomes 𝑓: 0.27 ( 47482 hom. )

Consequence

CCBE1
NM_133459.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0620

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:

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=-0.85).

BP6

Variant 18-59480160-G-T is Benign according to our data. Variant chr18-59480160-G-T is described in ClinVar as [Benign]. Clinvar id is 262350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCBE1	NM_133459.4 link	c.265+26C>A		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 link	c.265+26C>A		intron_variant		1	NM_133459.4	ENSP00000404464.2		Q6UXH8-1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42627

AN:

151966

Hom.:

6017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.266

AC:

65452

AN:

246022

Hom.:

8876

AF XY:

0.262

AC XY:

34895

AN XY:

133184

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.268

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.220

Gnomad SAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.285

Gnomad OTH exome

AF:

0.275

GnomAD4 exome

AF:

0.268

AC:

338373

AN:

1261354

Hom.:

47482

Cov.:

AF XY:

0.267

AC XY:

170639

AN XY:

638258

show subpopulations

Gnomad4 AFR exome

AF:

0.271

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.207

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.277

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.280

AC:

42652

AN:

152084

Hom.:

6018

Cov.:

AF XY:

0.276

AC XY:

20552

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.269

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.215

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.279

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.281

Hom.:

1137

Bravo

AF:

0.283

Asia WGS

AF:

0.214

AC:

744

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

DANN

Benign

0.41

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