rs644856

chr18-59470026-G-Achr18-59470026-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133459.4(CCBE1):c.266-419C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,960 control chromosomes in the GnomAD database, including 13,839 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 0.42 (13839 hom., cov: 31)
• Consequence: CCBE1 NM_133459.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCBE1	NM_133459.4	c.266-419C>T		intron_variant		ENST00000439986.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCBE1	ENST00000439986.9	c.266-419C>T		intron_variant		1	NM_133459.4	P1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64224 AN: 151842 Hom.: 13816 Cov.: 31

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.423 AC: 64291 AN: 151960 Hom.: 13839 Cov.: 31 AF XY: 0.426 AC XY: 31629 AN XY: 74222

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.426

Alfa AF: 0.452 Hom.: 7438

Bravo AF: 0.406

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.56
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

Other links and lift over

dbSNP: rs644856; hg19: chr18-57137258;