18-59642053-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCBE1	NM_133459.4	c.212+54576C>G		intron_variant		ENST00000439986.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCBE1	ENST00000439986.9	c.212+54576C>G		intron_variant		1	NM_133459.4	P1

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

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.397

Alfa AF: 0.382 Hom.: 611

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.45
Dann	Benign	0.14

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: rs2043041; hg19: chr18-57309285;