rs12891713

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001080414.4(CCDC88C):c.4107G>A(p.Gln1369Gln) 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

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

hydrocephalus, nonsyndromic, autosomal recessive 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
spinocerebellar ataxia type 40
Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

CCDC88C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.4107G>A	p.Gln1369Gln	synonymous_variant	Exon 23 of 30	ENST00000389857.11	NP_001073883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11 link	c.4107G>A	p.Gln1369Gln	synonymous_variant	Exon 23 of 30	5	NM_001080414.4	ENSP00000374507.6

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

GnomAD2 exomes

AF:

0.138

AC:

34334

AN:

249262

AF XY:

0.128

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 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

African (AFR)

AF:

0.448

AC:

14997

AN:

33470

American (AMR)

AF:

0.163

AC:

7268

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

4043

AN:

26134

East Asian (EAS)

AF:

0.0784

AC:

3111

AN:

39698

South Asian (SAS)

AF:

0.0717

AC:

6183

AN:

86254

European-Finnish (FIN)

AF:

0.123

AC:

6561

AN:

53386

Middle Eastern (MID)

AF:

0.148

AC:

853

AN:

5766

European-Non Finnish (NFE)

AF:

0.120

AC:

133803

AN:

1111668

Other (OTH)

AF:

0.138

AC:

8346

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

8022

16044

24065

32087

40109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5126

10252

15378

20504

25630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.210

AC:

31883

AN:

152156

Hom.:

4915

Cov.:

AF XY:

0.202

AC XY:

15023

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.439

AC:

18193

AN:

41462

American (AMR)

AF:

0.168

AC:

2576

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

534

AN:

3468

East Asian (EAS)

AF:

0.0895

AC:

464

AN:

5186

South Asian (SAS)

AF:

0.0683

AC:

330

AN:

4830

European-Finnish (FIN)

AF:

0.115

AC:

1220

AN:

10594

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

8030

AN:

68000

Other (OTH)

AF:

0.208

AC:

440

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1141

2282

3422

4563

5704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.152

Hom.:

3477

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

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.3

(source)

DANN

Benign

0.64

PhyloP100

0.080

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over