18-59642053-G-C

Variant names:

• chr18-59642053-G-C
• rs2043041
• NM_133459.4:c.212+54576C>G

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>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,170 control chromosomes in the GnomAD database, including 15,490 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 0.43 (15490 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 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>G		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>G		intron	N/A	ENSP00000404464.2	Q6UXH8-1
	CCBE1	ENST00000695904.1		c.212+54576C>G		intron	N/A	ENSP00000512259.1	A0A8Q3WKU1
	CCBE1	ENST00000649564.1		c.212+54576C>G		intron	N/A	ENSP00000497183.1	Q6UXH8-1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65920 AN: 152050 Hom.: 15465 Cov.: 31

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.434 AC: 65999 AN: 152170 Hom.: 15490 Cov.: 31 AF XY: 0.435 AC XY: 32365 AN XY: 74402

African (AFR) AF: 0.609 AC: 25265 AN: 41506

American (AMR) AF: 0.443 AC: 6764 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3470

East Asian (EAS) AF: 0.592 AC: 3064 AN: 5176

South Asian (SAS) AF: 0.390 AC: 1877 AN: 4808

European-Finnish (FIN) AF: 0.378 AC: 4009 AN: 10600

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22866 AN: 68008

Other (OTH) AF: 0.397 AC: 839 AN: 2116

Alfa AF: 0.382 Hom.: 611

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.45
DANN	Benign	0.14
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;