Variant rs112211533 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080414.4(CCDC88C):c.3636-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,604,306 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 62 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 57 hom. )

Consequence

CCDC88C
NM_001080414.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.00600

Variant links:

Genes affected

CCDC88C (HGNC:19967): (coiled-coil domain containing 88C) This gene encodes a ubiquitously expressed coiled-coil domain-containing protein that interacts with the dishevelled protein and is a negative regulator of the Wnt signalling pathway. The protein encoded by this gene has a PDZ-domain binding motif in its C-terminus with which it interacts with the dishevelled protein. Dishevelled is a scaffold protein involved in the regulation of the Wnt signaling pathway. The Wnt signaling pathway plays an important role in embryonic development, tissue maintenance, and cancer progression. Mutations in this gene cause autosomal recessive, primary non-syndromic congenital hydrocephalus; a condition characterized by excessive accumulation of cerebrospinal fluid in the ventricles of the brain. [provided by RefSeq, Jan 2013]

CCDC88C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 14-91300084-G-A is Benign according to our data. Variant chr14-91300084-G-A is described in ClinVar as [Benign]. Clinvar id is 158109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC88C	NM_001080414.4 linkuse as main transcript	c.3636-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000389857.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC88C	ENST00000389857.11 linkuse as main transcript	c.3636-14C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001080414.4	P1	Q9P219-1

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2364

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0542

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00381

AC:

876

AN:

230088

Hom.:

AF XY:

0.00284

AC XY:

355

AN XY:

125160

show subpopulations

Gnomad AFR exome

AF:

0.0575

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000142

Gnomad FIN exome

AF:

0.000104

Gnomad NFE exome

AF:

0.000173

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00158

AC:

2299

AN:

1451930

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

976

AN XY:

721404

show subpopulations

Gnomad4 AFR exome

AF:

0.0552

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000142

Gnomad4 FIN exome

AF:

0.000117

Gnomad4 NFE exome

AF:

0.0000839

Gnomad4 OTH exome

AF:

0.00357

GnomAD4 genome

AF:

0.0157

AC:

2393

AN:

152376

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1159

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0548

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00842

Hom.:

Bravo

AF:

0.0177

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.29

DANN

Benign

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over