rs1663549

chr18-59480160-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0620

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]

ACMG classification

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	UniProt
CCBE1	NM_133459.4	c.265+26C>A		intron_variant		ENST00000439986.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCBE1	ENST00000439986.9	c.265+26C>A		intron_variant		1	NM_133459.4	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42627 AN: 151966 Hom.: 6017 Cov.: 33

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

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.: 18 AF XY: 0.267 AC XY: 170639 AN XY: 638258

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.: 33 AF XY: 0.276 AC XY: 20552 AN XY: 74356

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:3

Revision: criteria provided, multiple submitters, no conflicts

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

not provided Benign:1

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

Other links and lift over

dbSNP: rs1663549; hg19: chr18-57147392;