Variant chr14-91297293-C-T 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.3966+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,608,290 control chromosomes in the GnomAD database, including 225,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24191 hom., cov: 33)

Exomes 𝑓: 0.52 ( 201724 hom. )

Consequence

CCDC88C
NM_001080414.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.328

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 14-91297293-C-T is Benign according to our data. Variant chr14-91297293-C-T is described in ClinVar as [Benign]. Clinvar id is 158110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-91297293-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 linkuse as main transcript	c.3966+12G>A		intron_variant		ENST00000389857.11	NP_001073883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11 linkuse as main transcript	c.3966+12G>A		intron_variant		5	NM_001080414.4	ENSP00000374507	P1	Q9P219-1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84557

AN:

152044

Hom.:

24177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.672

Gnomad AMI

AF:

0.593

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.534

Gnomad EAS

AF:

0.408

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.534

GnomAD3 exomes

AF:

0.498

AC:

119815

AN:

240752

Hom.:

30752

AF XY:

0.488

AC XY:

63707

AN XY:

130642

show subpopulations

Gnomad AFR exome

AF:

0.677

Gnomad AMR exome

AF:

0.453

Gnomad ASJ exome

AF:

0.531

Gnomad EAS exome

AF:

0.410

Gnomad SAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.549

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.515

GnomAD4 exome

AF:

0.522

AC:

760195

AN:

1456128

Hom.:

201724

Cov.:

AF XY:

0.515

AC XY:

372833

AN XY:

723756

show subpopulations

Gnomad4 AFR exome

AF:

0.672

Gnomad4 AMR exome

AF:

0.456

Gnomad4 ASJ exome

AF:

0.531

Gnomad4 EAS exome

AF:

0.431

Gnomad4 SAS exome

AF:

0.308

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.538

Gnomad4 OTH exome

AF:

0.520

GnomAD4 genome

AF:

0.556

AC:

84616

AN:

152162

Hom.:

24191

Cov.:

AF XY:

0.546

AC XY:

40613

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.672

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.534

Gnomad4 EAS

AF:

0.409

Gnomad4 SAS

AF:

0.290

Gnomad4 FIN

AF:

0.544

Gnomad4 NFE

AF:

0.538

Gnomad4 OTH

AF:

0.533

Alfa

AF:

0.527

Hom.:

11172

Bravo

AF:

0.560

Asia WGS

AF:

0.379

AC:

1320

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -
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

- -

Spinocerebellar ataxia type 40

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Hydrocephalus, nonsyndromic, autosomal recessive 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.8

DANN

Benign

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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