rs8082983

Variant names:

• chr18-59488486-A-G
• rs8082983
• NM_133459.4:c.213-8248T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCBE1	NM_133459.4	c.213-8248T>C		intron_variant	Intron 2 of 10	ENST00000439986.9	NP_597716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCBE1	ENST00000439986.9	c.213-8248T>C		intron_variant	Intron 2 of 10	1	NM_133459.4	ENSP00000404464.2

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

African (AFR) AF: 0.492 AC: 20406 AN: 41486

American (AMR) AF: 0.450 AC: 6869 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1122 AN: 3464

East Asian (EAS) AF: 0.831 AC: 4289 AN: 5162

South Asian (SAS) AF: 0.456 AC: 2190 AN: 4802

European-Finnish (FIN) AF: 0.342 AC: 3609 AN: 10554

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22835 AN: 67950

Other (OTH) AF: 0.417 AC: 883 AN: 2116

Alfa AF: 0.354 Hom.: 5137

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
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

Other links and lift over

dbSNP: rs8082983; hg19: chr18-57155718;