rs7242532

Variant names:

• chr18-59445872-C-T
• rs7242532
• NM_133459.4:c.775+2111G>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.775+2111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,134 control chromosomes in the GnomAD database, including 7,874 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 0.32 (7874 hom., cov: 32)
• Consequence: CCBE1 NM_133459.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.90
• 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 (AMR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCBE1	NM_133459.4	c.775+2111G>A		intron_variant	Intron 7 of 10	ENST00000439986.9	NP_597716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCBE1	ENST00000439986.9	c.775+2111G>A		intron_variant	Intron 7 of 10	1	NM_133459.4	ENSP00000404464.2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48377 AN: 152016 Hom.: 7854 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.318 AC: 48442 AN: 152134 Hom.: 7874 Cov.: 32 AF XY: 0.319 AC XY: 23696 AN XY: 74380

African (AFR) AF: 0.325 AC: 13505 AN: 41502

American (AMR) AF: 0.339 AC: 5179 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1438 AN: 5168

South Asian (SAS) AF: 0.212 AC: 1025 AN: 4826

European-Finnish (FIN) AF: 0.335 AC: 3542 AN: 10578

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21889 AN: 67996

Other (OTH) AF: 0.334 AC: 705 AN: 2112

Alfa AF: 0.315 Hom.: 23535

Bravo AF: 0.322

Asia WGS AF: 0.252 AC: 875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.068
DANN	Benign	0.51
PhyloP100		-4.9
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: rs7242532; hg19: chr18-57113104;