Variant rs12891713 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001080414.4(CCDC88C):c.4107G>A(p.Gln1369=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,613,610 control chromosomes in the GnomAD database, including 18,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4915 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13960 hom. )

Consequence

CCDC88C
NM_001080414.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0800

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 14-91294178-C-T is Benign according to our data. Variant chr14-91294178-C-T is described in ClinVar as [Benign]. Clinvar id is 158112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 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.4107G>A	p.Gln1369=	synonymous_variant	23/30	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.4107G>A	p.Gln1369=	synonymous_variant	23/30	5	NM_001080414.4	ENSP00000374507	P1	Q9P219-1

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31805

AN:

152038

Hom.:

4884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.438

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.0893

Gnomad SAS

AF:

0.0699

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.207

GnomAD3 exomes

AF:

0.138

AC:

34334

AN:

249262

Hom.:

3283

AF XY:

0.128

AC XY:

17306

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.451

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.0913

Gnomad SAS exome

AF:

0.0713

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.127

AC:

185165

AN:

1461454

Hom.:

13960

Cov.:

AF XY:

0.124

AC XY:

89829

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.448

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.0784

Gnomad4 SAS exome

AF:

0.0717

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.210

AC:

31883

AN:

152156

Hom.:

4915

Cov.:

AF XY:

0.202

AC XY:

15023

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.439

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.0895

Gnomad4 SAS

AF:

0.0683

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.208

Alfa

AF:

0.156

Hom.:

2228

Bravo

AF:

0.227

Asia WGS

AF:

0.137

AC:

477

AN:

3478

EpiCase

AF:

0.116

EpiControl

AF:

0.115

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

-0.43

CADD

Benign

7.3

DANN

Benign

0.64

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