chr18-59431510-G-T

Variant names:

• chr18-59431510-G-T
• rs6567083
• NM_133459.4:c.*4398C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_133459.4(CCBE1):​c.*4398C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,098 control chromosomes in the GnomAD database, including 52,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52624 hom., cov: 31)
  • Exomes 𝑓: 0.96 (12 hom.)
• Consequence: CCBE1 NM_133459.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.744
• Publications: 2 publications found

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]

CCBE1 Gene-Disease associations (from GenCC):

• Hennekam lymphangiectasia-lymphedema syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• Hennekam syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-59431510-G-T is Benign according to our data. Variant chr18-59431510-G-T is described in ClinVar as Benign. ClinVar VariationId is 327597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133459.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCBE1	NM_133459.4	MANE Select	c.*4398C>A		3_prime_UTR	Exon 11 of 11	NP_597716.1	Q6UXH8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCBE1	ENST00000439986.9	TSL:1 MANE Select	c.*4398C>A		3_prime_UTR	Exon 11 of 11	ENSP00000404464.2	Q6UXH8-1
	CCBE1	ENST00000649564.1		c.*4398C>A		3_prime_UTR	Exon 12 of 12	ENSP00000497183.1	Q6UXH8-1
	CCBE1	ENST00000650467.2		c.*4398C>A		3_prime_UTR	Exon 9 of 9	ENSP00000496897.2	A0A3B3IRL6

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126252 AN: 151954 Hom.: 52584 Cov.: 31

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.809

GnomAD4 exome AF: 0.962 AC: 25 AN: 26 Hom.: 12 Cov.: 0 AF XY: 0.938 AC XY: 15 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.950 AC: 19 AN: 20

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.831 AC: 126350 AN: 152072 Hom.: 52624 Cov.: 31 AF XY: 0.829 AC XY: 61581 AN XY: 74328

African (AFR) AF: 0.890 AC: 36941 AN: 41494

American (AMR) AF: 0.803 AC: 12265 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2828 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4554 AN: 5160

South Asian (SAS) AF: 0.909 AC: 4379 AN: 4816

European-Finnish (FIN) AF: 0.761 AC: 8022 AN: 10542

Middle Eastern (MID) AF: 0.849 AC: 248 AN: 292

European-Non Finnish (NFE) AF: 0.804 AC: 54663 AN: 68002

Other (OTH) AF: 0.811 AC: 1711 AN: 2110

Alfa AF: 0.800 Hom.: 3196

Bravo AF: 0.833

Asia WGS AF: 0.893 AC: 3106 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hennekam lymphangiectasia-lymphedema syndrome 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.38
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6567083; hg19: chr18-57098742;