rs11152166

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCBE1	NM_133459.4	c.212+49054G>A		intron_variant	Intron 2 of 10	ENST00000439986.9	NP_597716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCBE1	ENST00000439986.9	c.212+49054G>A		intron_variant	Intron 2 of 10	1	NM_133459.4	ENSP00000404464.2

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

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.477

Alfa AF: 0.557 Hom.: 31555

Bravo AF: 0.440

Asia WGS AF: 0.401 AC: 1396 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs11152166; hg19: chr18-57314807;