rs7160325

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001080414.4(CCDC88C):c.1773G>A(p.Glu591Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00767 in 1,613,864 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 58 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 93 hom. )

Consequence

CCDC88C
NM_001080414.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.36

Publications

1 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 14-91314043-C-T is Benign according to our data. Variant chr14-91314043-C-T is described in ClinVar as Benign. ClinVar VariationId is 158092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.1773G>A	p.Glu591Glu	synonymous_variant	Exon 15 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.1773G>A	p.Glu591Glu	synonymous_variant	Exon 15 of 30	5	NM_001080414.4	ENSP00000374507.6
CCDC88C	ENST00000557507.1 link	n.329G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2912

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0542

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00953

Gnomad FIN

AF:

0.00528

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.00416

Gnomad OTH

AF:

0.0182

GnomAD2 exomes

AF:

0.00966

AC:

2407

AN:

249152

AF XY:

0.00944

show subpopulations

Gnomad AFR exome

AF:

0.0566

Gnomad AMR exome

AF:

0.00724

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00539

Gnomad NFE exome

AF:

0.00532

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.00646

AC:

9444

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00651

AC XY:

4734

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.0563

AC:

1884

AN:

33480

American (AMR)

AF:

0.00785

AC:

351

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0163

AC:

427

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0102

AC:

883

AN:

86256

European-Finnish (FIN)

AF:

0.00476

AC:

254

AN:

53382

Middle Eastern (MID)

AF:

0.0272

AC:

157

AN:

5768

European-Non Finnish (NFE)

AF:

0.00436

AC:

4847

AN:

1111852

Other (OTH)

AF:

0.0106

AC:

639

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

557

1114

1672

2229

2786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

234

468

702

936

1170

<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:

0.0193

AC:

2937

AN:

152194

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

1393

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0547

AC:

2270

AN:

41496

American (AMR)

AF:

0.0122

AC:

186

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00912

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00528

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00416

AC:

283

AN:

68002

Other (OTH)

AF:

0.0180

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

144

288

433

577

721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0109

Hom.:

Bravo

AF:

0.0219

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.00583

EpiControl

AF:

0.00664

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

- -

Jan 23, 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

-0.49

CADD

Benign

8.4

(source)

DANN

Benign

0.58

PhyloP100

1.4

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