14-91307224-T-C

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.3009A>G(p.Leu1003Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,612,236 control chromosomes in the GnomAD database, including 260,807 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23643 hom., cov: 32)

Exomes 𝑓: 0.57 ( 237164 hom. )

Consequence

CCDC88C
NM_001080414.4 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0160

Publications

20 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
spinocerebellar ataxia type 40
Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

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=-0.59).

BP6

Variant 14-91307224-T-C is Benign according to our data. Variant chr14-91307224-T-C is described in ClinVar as Benign. ClinVar VariationId is 158098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.016 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080414.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC88C	NM_001080414.4	MANE Select	c.3009A>G	p.Leu1003Leu	splice_region synonymous	Exon 18 of 30	NP_001073883.2	Q9P219-1
CCDC88C	NR_189158.1		n.3139A>G		splice_region non_coding_transcript_exon	Exon 18 of 31
CCDC88C	NR_189159.1		n.3139A>G		splice_region non_coding_transcript_exon	Exon 18 of 31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	ENST00000389857.11	TSL:5 MANE Select	c.3009A>G	p.Leu1003Leu	splice_region synonymous	Exon 18 of 30	ENSP00000374507.6	Q9P219-1

Frequencies

GnomAD3 genomes

AF:

0.555

AC:

84312

AN:

151984

Hom.:

23633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.628

Gnomad AMR

AF:

0.495

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.523

GnomAD2 exomes

AF:

0.532

AC:

132116

AN:

248246

AF XY:

0.526

show subpopulations

Gnomad AFR exome

AF:

0.546

Gnomad AMR exome

AF:

0.518

Gnomad ASJ exome

AF:

0.508

Gnomad EAS exome

AF:

0.367

Gnomad FIN exome

AF:

0.626

Gnomad NFE exome

AF:

0.584

Gnomad OTH exome

AF:

0.550

GnomAD4 exome

AF:

0.566

AC:

826433

AN:

1460134

Hom.:

237164

Cov.:

AF XY:

0.560

AC XY:

406632

AN XY:

726404

show subpopulations

African (AFR)

AF:

0.542

AC:

18128

AN:

33466

American (AMR)

AF:

0.514

AC:

22981

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

13309

AN:

26130

East Asian (EAS)

AF:

0.395

AC:

15693

AN:

39694

South Asian (SAS)

AF:

0.388

AC:

33441

AN:

86242

European-Finnish (FIN)

AF:

0.627

AC:

32942

AN:

52518

Middle Eastern (MID)

AF:

0.508

AC:

2897

AN:

5700

European-Non Finnish (NFE)

AF:

0.589

AC:

654190

AN:

1111340

Other (OTH)

AF:

0.544

AC:

32852

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

17957

35914

53871

71828

89785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17892

35784

53676

71568

89460

<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:

0.555

AC:

84369

AN:

152102

Hom.:

23643

Cov.:

AF XY:

0.549

AC XY:

40805

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.548

AC:

22744

AN:

41476

American (AMR)

AF:

0.495

AC:

7567

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

1807

AN:

3470

East Asian (EAS)

AF:

0.367

AC:

1899

AN:

5174

South Asian (SAS)

AF:

0.390

AC:

1882

AN:

4820

European-Finnish (FIN)

AF:

0.633

AC:

6689

AN:

10572

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.588

AC:

39955

AN:

67986

Other (OTH)

AF:

0.520

AC:

1099

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1971

3941

5912

7882

9853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.562

Hom.:

40784

Bravo

AF:

0.545

Asia WGS

AF:

0.399

AC:

1393

AN:

3478

EpiCase

AF:

0.567

EpiControl

AF:

0.565

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hydrocephalus, nonsyndromic, autosomal recessive 1 (1)

not specified (1)

Spinocerebellar ataxia type 40 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.0

(source)

DANN

Benign

0.36

PhyloP100

-0.016

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over