18-59431481-TG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_133459.4(CCBE1):c.*4426del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (24005 hom., cov: 0)
  • Exomes 𝑓: 0.70 (3 hom.)
• Consequence: CCBE1 NM_133459.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.218

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 -10 ACMG points.

• BP6: Variant 18-59431481-TG-T is Benign according to our data. Variant chr18-59431481-TG-T is described in ClinVar as [Benign]. Clinvar id is 327596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCBE1	NM_133459.4	c.*4426del		3_prime_UTR_variant	11/11	ENST00000439986.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCBE1	ENST00000439986.9	c.*4426del		3_prime_UTR_variant	11/11	1	NM_133459.4	P1
CCBE1	ENST00000649564.1	c.*4426del		3_prime_UTR_variant	12/12			P1
CCBE1	ENST00000650467.2	c.*4426del		3_prime_UTR_variant	9/9

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85233 AN: 151826 Hom.: 23993 Cov.: 0

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.551

GnomAD4 exome AF: 0.700 AC: 7 AN: 10 Hom.: 3 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.561 AC: 85286 AN: 151944 Hom.: 24005 Cov.: 0 AF XY: 0.565 AC XY: 41952 AN XY: 74264

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.549

Alfa AF: 0.573 Hom.: 3089

Bravo AF: 0.556

Asia WGS AF: 0.596 AC: 2071 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hennekam lymphangiectasia-lymphedema syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs66482821; hg19: chr18-57098713;