18-59471725-T-C

Position:

• chr18-59471725-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133459.4(CCBE1):​c.266-2118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,134 control chromosomes in the GnomAD database, including 5,604 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 0.26 (5604 hom., cov: 33)
• Consequence: CCBE1 NM_133459.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCBE1	NM_133459.4	c.266-2118A>G		intron_variant		ENST00000439986.9	NP_597716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCBE1	ENST00000439986.9	c.266-2118A>G		intron_variant		1	NM_133459.4	ENSP00000404464	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39171 AN: 152016 Hom.: 5599 Cov.: 33

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.258 AC: 39190 AN: 152134 Hom.: 5604 Cov.: 33 AF XY: 0.253 AC XY: 18825 AN XY: 74370

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.244

Alfa AF: 0.227 Hom.: 6237

Bravo AF: 0.265

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.9
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs12961264; hg19: chr18-57138957;