rs4940465

Positions:

• chr18-59506612-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.213-26374A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,102 control chromosomes in the GnomAD database, including 5,504 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 (5504 hom., cov: 32)
• Consequence: CCBE1 NM_133459.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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 (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCBE1	NM_133459.4	c.213-26374A>G		intron_variant		ENST00000439986.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCBE1	ENST00000439986.9	c.213-26374A>G		intron_variant		1	NM_133459.4	P1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40056 AN: 151984 Hom.: 5502 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.263 AC: 40067 AN: 152102 Hom.: 5504 Cov.: 32 AF XY: 0.260 AC XY: 19319 AN XY: 74352

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.271

Alfa AF: 0.285 Hom.: 8140

Bravo AF: 0.265

Asia WGS AF: 0.228 AC: 794 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	0.38
DANN	Benign	0.69

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: rs4940465; hg19: chr18-57173844; COSMIC: COSV71671253;