NM_133459.4:c.212+54576C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_133459.4(CCBE1):​c.212+54576C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,168 control chromosomes in the GnomAD database, including 17,205 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 17205 hom., cov: 31)

Consequence

CCBE1
NM_133459.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.235

Publications

1 publications found
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 Gene-Disease associations (from GenCC):
  • Hennekam lymphangiectasia-lymphedema syndrome 1
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • Hennekam syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.04).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCBE1NM_133459.4 linkc.212+54576C>A intron_variant Intron 2 of 10 ENST00000439986.9 NP_597716.1 Q6UXH8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCBE1ENST00000439986.9 linkc.212+54576C>A intron_variant Intron 2 of 10 1 NM_133459.4 ENSP00000404464.2 Q6UXH8-1

Frequencies

GnomAD3 genomes
AF:
0.452
AC:
68728
AN:
152050
Hom.:
17204
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.247
Gnomad AMI
AF:
0.658
Gnomad AMR
AF:
0.476
Gnomad ASJ
AF:
0.509
Gnomad EAS
AF:
0.221
Gnomad SAS
AF:
0.450
Gnomad FIN
AF:
0.575
Gnomad MID
AF:
0.557
Gnomad NFE
AF:
0.563
Gnomad OTH
AF:
0.487
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.452
AC:
68741
AN:
152168
Hom.:
17205
Cov.:
31
AF XY:
0.452
AC XY:
33651
AN XY:
74384
show subpopulations
African (AFR)
AF:
0.247
AC:
10250
AN:
41516
American (AMR)
AF:
0.475
AC:
7267
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.509
AC:
1767
AN:
3470
East Asian (EAS)
AF:
0.222
AC:
1147
AN:
5178
South Asian (SAS)
AF:
0.451
AC:
2166
AN:
4802
European-Finnish (FIN)
AF:
0.575
AC:
6097
AN:
10596
Middle Eastern (MID)
AF:
0.554
AC:
163
AN:
294
European-Non Finnish (NFE)
AF:
0.563
AC:
38266
AN:
68002
Other (OTH)
AF:
0.482
AC:
1019
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1796
3593
5389
7186
8982
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
616
1232
1848
2464
3080
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.508
Hom.:
611

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.43
DANN
Benign
0.26
PhyloP100
-0.23
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2043041; hg19: chr18-57309285; API