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rs632899

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

2

Clinical Significance

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

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]

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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 UniProt
CCBE1NM_133459.4 linkuse as main transcriptc.266-30T>C intron_variant ENST00000439986.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCBE1ENST00000439986.9 linkuse as main transcriptc.266-30T>C intron_variant 1 NM_133459.4 P1Q6UXH8-1

Frequencies

GnomAD3 genomes
AF:
0.450
AC:
68395
AN:
151980
Hom.:
15397
Cov.:
33
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.:
46
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.:
33
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:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJan 24, 2024This 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. -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -
Hennekam lymphangiectasia-lymphedema syndrome 1 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 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.

Other links and lift over

dbSNP: rs632899; hg19: chr18-57136869; COSMIC: COSV67950242; COSMIC: COSV67950242; API