rs8082983

Positions:

• chr18-59488486-A-G

Variant summary

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

The NM_133459.4(CCBE1):​c.213-8248T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,016 control chromosomes in the GnomAD database, including 13,915 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 0.41 (13915 hom., cov: 32)
• Consequence: CCBE1 NM_133459.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCBE1	NM_133459.4	c.213-8248T>C		intron_variant		ENST00000439986.9	NP_597716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCBE1	ENST00000439986.9	c.213-8248T>C		intron_variant		1	NM_133459.4	ENSP00000404464	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62713 AN: 151898 Hom.: 13906 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.413 AC: 62760 AN: 152016 Hom.: 13915 Cov.: 32 AF XY: 0.418 AC XY: 31027 AN XY: 74302

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.417

Alfa AF: 0.354 Hom.: 4670

Bravo AF: 0.430

Asia WGS AF: 0.618 AC: 2147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.39

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: rs8082983; hg19: chr18-57155718;