chr14-91416785-G-A

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.114C>T(p.Tyr38Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,612,464 control chromosomes in the GnomAD database, including 41,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2774 hom., cov: 32)

Exomes 𝑓: 0.22 ( 38875 hom. )

Consequence

CCDC88C
NM_001080414.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.461

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 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 14-91416785-G-A is Benign according to our data. Variant chr14-91416785-G-A is described in ClinVar as [Benign]. Clinvar id is 158090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.461 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.114C>T	p.Tyr38Tyr	synonymous_variant	Exon 2 of 30	ENST00000389857.11	NP_001073883.2	Q9P219-1B4DZB8
CCDC88C	XM_011536796.3 link	c.6C>T	p.Tyr2Tyr	synonymous_variant	Exon 2 of 30		XP_011535098.1
CCDC88C	NR_189158.1 link	n.244C>T		non_coding_transcript_exon_variant	Exon 2 of 31
CCDC88C	NR_189159.1 link	n.244C>T		non_coding_transcript_exon_variant	Exon 2 of 31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11 link	c.114C>T	p.Tyr38Tyr	synonymous_variant	Exon 2 of 30	5	NM_001080414.4	ENSP00000374507.6		Q9P219-1

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25993

AN:

152006

Hom.:

2778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0814

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.0249

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.167

GnomAD2 exomes

AF:

0.171

AC:

42367

AN:

247748

AF XY:

0.175

show subpopulations

Gnomad AFR exome

AF:

0.0796

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.0270

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.222

AC:

324461

AN:

1460342

Hom.:

38875

Cov.:

AF XY:

0.220

AC XY:

159505

AN XY:

726512

show subpopulations

African (AFR)

AF:

0.0721

AC:

2412

AN:

33468

American (AMR)

AF:

0.108

AC:

4845

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

4525

AN:

26126

East Asian (EAS)

AF:

0.0335

AC:

1331

AN:

39698

South Asian (SAS)

AF:

0.138

AC:

11868

AN:

86190

European-Finnish (FIN)

AF:

0.157

AC:

8344

AN:

53290

Middle Eastern (MID)

AF:

0.120

AC:

691

AN:

5766

European-Non Finnish (NFE)

AF:

0.251

AC:

278538

AN:

1110798

Other (OTH)

AF:

0.197

AC:

11907

AN:

60340

Heterozygous variant carriers

11617

23235

34852

46470

58087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

9142

18284

27426

36568

45710

<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:

0.171

AC:

25989

AN:

152122

Hom.:

2774

Cov.:

AF XY:

0.163

AC XY:

12125

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0812

AC:

3369

AN:

41492

American (AMR)

AF:

0.150

AC:

2300

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

623

AN:

3470

East Asian (EAS)

AF:

0.0249

AC:

129

AN:

5178

South Asian (SAS)

AF:

0.130

AC:

626

AN:

4820

European-Finnish (FIN)

AF:

0.144

AC:

1521

AN:

10582

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16847

AN:

67978

Other (OTH)

AF:

0.165

AC:

348

AN:

2108

Heterozygous variant carriers

1099

2198

3297

4396

5495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<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:

0.209

Hom.:

3042

Bravo

AF:

0.164

Asia WGS

AF:

0.0760

AC:

263

AN:

3478

EpiCase

AF:

0.234

EpiControl

AF:

0.229

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

May 04, 2021

GeneDx

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

- -

Spinocerebellar ataxia type 40

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hydrocephalus, nonsyndromic, autosomal recessive 1

Benign:1

Jul 14, 2021

Genome-Nilou Lab

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

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

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