rs7243244

Variant names:

• chr18-59509684-G-A
• rs7243244
• NM_133459.4:c.213-29446C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133459.4(CCBE1):​c.213-29446C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,974 control chromosomes in the GnomAD database, including 9,044 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 0.34 (9044 hom., cov: 32)
• Consequence: CCBE1 NM_133459.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Hennekam syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCBE1	NM_133459.4	c.213-29446C>T		intron_variant	Intron 2 of 10	ENST00000439986.9	NP_597716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCBE1	ENST00000439986.9	c.213-29446C>T		intron_variant	Intron 2 of 10	1	NM_133459.4	ENSP00000404464.2

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50890 AN: 151856 Hom.: 9036 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.335 AC: 50918 AN: 151974 Hom.: 9044 Cov.: 32 AF XY: 0.332 AC XY: 24679 AN XY: 74280

African (AFR) AF: 0.429 AC: 17754 AN: 41426

American (AMR) AF: 0.275 AC: 4204 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1006 AN: 3472

East Asian (EAS) AF: 0.494 AC: 2552 AN: 5164

South Asian (SAS) AF: 0.228 AC: 1096 AN: 4800

European-Finnish (FIN) AF: 0.291 AC: 3066 AN: 10536

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20040 AN: 67970

Other (OTH) AF: 0.327 AC: 692 AN: 2114

Alfa AF: 0.309 Hom.: 23875

Bravo AF: 0.343

Asia WGS AF: 0.356 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.55
PhyloP100		-0.53
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: rs7243244; hg19: chr18-57176916;