NM_133459.4:c.212+49054G>A

Variant names:

• chr18-59647575-C-T
• rs11152166
• NM_133459.4:c.212+49054G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133459.4(CCBE1):​c.212+49054G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,994 control chromosomes in the GnomAD database, including 17,672 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 0.45 (17672 hom., cov: 33)
• Consequence: CCBE1 NM_133459.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCBE1	NM_133459.4	MANE Select	c.212+49054G>A		intron	N/A	NP_597716.1	Q6UXH8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCBE1	ENST00000439986.9	TSL:1 MANE Select	c.212+49054G>A		intron	N/A	ENSP00000404464.2	Q6UXH8-1
	CCBE1	ENST00000695904.1		c.212+49054G>A		intron	N/A	ENSP00000512259.1	A0A8Q3WKU1
	CCBE1	ENST00000649564.1		c.212+49054G>A		intron	N/A	ENSP00000497183.1	Q6UXH8-1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68488 AN: 151876 Hom.: 17657 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.451 AC: 68518 AN: 151994 Hom.: 17672 Cov.: 33 AF XY: 0.452 AC XY: 33569 AN XY: 74278

African (AFR) AF: 0.186 AC: 7728 AN: 41468

American (AMR) AF: 0.551 AC: 8421 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1574 AN: 3472

East Asian (EAS) AF: 0.403 AC: 2081 AN: 5168

South Asian (SAS) AF: 0.465 AC: 2238 AN: 4816

European-Finnish (FIN) AF: 0.547 AC: 5758 AN: 10520

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38943 AN: 67966

Other (OTH) AF: 0.477 AC: 1007 AN: 2112

Alfa AF: 0.546 Hom.: 38754

Bravo AF: 0.440

Asia WGS AF: 0.401 AC: 1396 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.76
PhyloP100		-0.71
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: rs11152166; hg19: chr18-57314807;