Variant rs4940876 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.401-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,598,734 control chromosomes in the GnomAD database, including 787,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.96 ( 70644 hom., cov: 34)

Exomes 𝑓: 1.0 ( 717311 hom. )

Consequence

CCBE1
ENST00000439986.9 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.566

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

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 18-59466920-A-G is Benign according to our data. Variant chr18-59466920-A-G is described in ClinVar as [Benign]. Clinvar id is 262353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.401-29T>C		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.401-29T>C		intron_variant		1	NM_133459.4	ENSP00000404464	P1	Q6UXH8-1

Frequencies

GnomAD3 genomes

AF:

0.962

AC:

146348

AN:

152208

Hom.:

70593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.868

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.985

Gnomad ASJ

AF:

0.992

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.967

GnomAD3 exomes

AF:

0.989

AC:

248218

AN:

250914

Hom.:

122916

AF XY:

0.992

AC XY:

134538

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.867

Gnomad AMR exome

AF:

0.991

Gnomad ASJ exome

AF:

0.992

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.993

GnomAD4 exome

AF:

0.996

AC:

1440192

AN:

1446408

Hom.:

717311

Cov.:

AF XY:

0.996

AC XY:

717785

AN XY:

720536

show subpopulations

Gnomad4 AFR exome

AF:

0.871

Gnomad4 AMR exome

AF:

0.991

Gnomad4 ASJ exome

AF:

0.990

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.991

GnomAD4 genome

AF:

0.961

AC:

146459

AN:

152326

Hom.:

70644

Cov.:

AF XY:

0.963

AC XY:

71718

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.868

Gnomad4 AMR

AF:

0.985

Gnomad4 ASJ

AF:

0.992

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.967

Alfa

AF:

0.970

Hom.:

15139

Bravo

AF:

0.956

Asia WGS

AF:

0.992

AC:

3449

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 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. 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

3.6

DANN

Benign

0.75

BranchPoint Hunter

1.0

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