rs644856

Variant names:

• chr18-59470026-G-A
• rs644856
• NM_133459.4:c.266-419C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-59470026-G-A
• chr18-59470026-G-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.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
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133459.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCBE1	NM_133459.4	MANE Select	c.266-419C>T		intron	N/A	NP_597716.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCBE1	ENST00000439986.9	TSL:1 MANE Select	c.266-419C>T		intron	N/A	ENSP00000404464.2
	CCBE1	ENST00000695904.1		c.266-419C>T		intron	N/A	ENSP00000512259.1
	CCBE1	ENST00000649564.1		c.266-419C>T		intron	N/A	ENSP00000497183.1

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

African (AFR) AF: 0.350 AC: 14525 AN: 41468

American (AMR) AF: 0.381 AC: 5821 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1763 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2207 AN: 5132

South Asian (SAS) AF: 0.508 AC: 2446 AN: 4814

European-Finnish (FIN) AF: 0.481 AC: 5079 AN: 10550

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31163 AN: 67940

Other (OTH) AF: 0.426 AC: 900 AN: 2112

Alfa AF: 0.451 Hom.: 8291

Bravo AF: 0.406

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.36
PhyloP100		-0.60
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: rs644856; hg19: chr18-57137258;