rs7243244

Positions:

• chr18-59509684-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.99).
• 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/exons	MANE	UniProt
CCBE1	NM_133459.4	c.213-29446C>T		intron_variant		ENST00000439986.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCBE1	ENST00000439986.9	c.213-29446C>T		intron_variant		1	NM_133459.4	P1

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

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.327

Alfa AF: 0.305 Hom.: 14663

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

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: rs7243244; hg19: chr18-57176916;