Variant 18-59447971-T-C 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 ENST00000439986.9(CCBE1):c.775+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,613,712 control chromosomes in the GnomAD database, including 252,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27096 hom., cov: 32)

Exomes 𝑓: 0.55 ( 225031 hom. )

Consequence

CCBE1
ENST00000439986.9 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.719

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=-0.91).

BP6

Variant 18-59447971-T-C is Benign according to our data. Variant chr18-59447971-T-C is described in ClinVar as [Benign]. Clinvar id is 262355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-59447971-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 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.775+12A>G		intron_variant		ENST00000439986.9	NP_597716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCBE1	ENST00000439986.9 linkuse as main transcript	c.775+12A>G		intron_variant		1	NM_133459.4	ENSP00000404464	P1	Q6UXH8-1

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89598

AN:

151988

Hom.:

27051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.479

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.565

Gnomad OTH

AF:

0.579

GnomAD3 exomes

AF:

0.527

AC:

132204

AN:

251048

Hom.:

35688

AF XY:

0.524

AC XY:

71109

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.717

Gnomad AMR exome

AF:

0.491

Gnomad ASJ exome

AF:

0.606

Gnomad EAS exome

AF:

0.331

Gnomad SAS exome

AF:

0.471

Gnomad FIN exome

AF:

0.485

Gnomad NFE exome

AF:

0.557

Gnomad OTH exome

AF:

0.547

GnomAD4 exome

AF:

0.552

AC:

806905

AN:

1461606

Hom.:

225031

Cov.:

AF XY:

0.550

AC XY:

399590

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.725

Gnomad4 AMR exome

AF:

0.505

Gnomad4 ASJ exome

AF:

0.607

Gnomad4 EAS exome

AF:

0.348

Gnomad4 SAS exome

AF:

0.475

Gnomad4 FIN exome

AF:

0.488

Gnomad4 NFE exome

AF:

0.563

Gnomad4 OTH exome

AF:

0.554

GnomAD4 genome

AF:

0.590

AC:

89700

AN:

152106

Hom.:

27096

Cov.:

AF XY:

0.582

AC XY:

43281

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.717

Gnomad4 AMR

AF:

0.556

Gnomad4 ASJ

AF:

0.612

Gnomad4 EAS

AF:

0.337

Gnomad4 SAS

AF:

0.480

Gnomad4 FIN

AF:

0.484

Gnomad4 NFE

AF:

0.565

Gnomad4 OTH

AF:

0.579

Alfa

AF:

0.580

Hom.:

5328

Bravo

AF:

0.600

Asia WGS

AF:

0.449

AC:

1562

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 53% of total chromosomes in ExAC -
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 77% of patients studied by a panel of primary immunodeficiencies. Number of patients: 73. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Hennekam lymphangiectasia-lymphedema syndrome 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.8

DANN

Benign

0.36

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