18-59642053-G-T

Variant names:

• chr18-59642053-G-T
• rs2043041
• NM_133459.4:c.212+54576C>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+54576C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,168 control chromosomes in the GnomAD database, including 17,205 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 (17205 hom., cov: 31)
• Consequence: CCBE1 NM_133459.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• 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: 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 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+54576C>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+54576C>A		intron	N/A	ENSP00000404464.2	Q6UXH8-1
	CCBE1	ENST00000695904.1		c.212+54576C>A		intron	N/A	ENSP00000512259.1	A0A8Q3WKU1
	CCBE1	ENST00000649564.1		c.212+54576C>A		intron	N/A	ENSP00000497183.1	Q6UXH8-1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68728 AN: 152050 Hom.: 17204 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.452 AC: 68741 AN: 152168 Hom.: 17205 Cov.: 31 AF XY: 0.452 AC XY: 33651 AN XY: 74384

African (AFR) AF: 0.247 AC: 10250 AN: 41516

American (AMR) AF: 0.475 AC: 7267 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1767 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1147 AN: 5178

South Asian (SAS) AF: 0.451 AC: 2166 AN: 4802

European-Finnish (FIN) AF: 0.575 AC: 6097 AN: 10596

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38266 AN: 68002

Other (OTH) AF: 0.482 AC: 1019 AN: 2114

Alfa AF: 0.508 Hom.: 611

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.26
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: rs2043041; hg19: chr18-57309285;