18-59642053-G-T

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>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,168 control chromosomes in the GnomAD database, including 17,205 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 (17205 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68728 AN: 152050 Hom.: 17204 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.452 AC: 68741 AN: 152168 Hom.: 17205 Cov.: 31 AF XY: 0.452 AC XY: 33651 AN XY: 74384

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.482

Alfa AF: 0.508 Hom.: 611

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.43
Dann	Benign	0.26

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;