rs3742654

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080414.4(CCDC88C):c.60+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,580,304 control chromosomes in the GnomAD database, including 140,642 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12126 hom., cov: 31)

Exomes 𝑓: 0.42 ( 128516 hom. )

Consequence

CCDC88C
NM_001080414.4 splice_region, intron

Scores

Splicing: ADA: 0.00003065

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.126

Publications

9 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 14-91417623-G-T is Benign according to our data. Variant chr14-91417623-G-T is described in ClinVar as Benign. ClinVar VariationId is 158120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 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	Effect	Exon Rank	Protein	UniProt
CCDC88C	NM_001080414.4	MANE Select	c.60+8C>A	splice_region intron	N/A	NP_001073883.2	Q9P219-1
CCDC88C	NR_189158.1		n.190+8C>A	splice_region intron	N/A
CCDC88C	NR_189159.1		n.190+8C>A	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC88C	ENST00000389857.11	TSL:5 MANE Select	c.60+8C>A	splice_region intron	N/A	ENSP00000374507.6	Q9P219-1
CCDC88C	ENST00000553403.1	TSL:1	c.60+8C>A	splice_region intron	N/A	ENSP00000451392.1	G3V3S0
CCDC88C	ENST00000554165.1	TSL:3	n.48+8C>A	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58836

AN:

151608

Hom.:

12125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.376

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.384

GnomAD2 exomes

AF:

0.415

AC:

84912

AN:

204568

AF XY:

0.419

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.351

Gnomad ASJ exome

AF:

0.421

Gnomad EAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.612

Gnomad NFE exome

AF:

0.413

Gnomad OTH exome

AF:

0.415

GnomAD4 exome

AF:

0.420

AC:

600647

AN:

1428588

Hom.:

128516

Cov.:

AF XY:

0.422

AC XY:

299283

AN XY:

709930

show subpopulations

African (AFR)

AF:

0.276

AC:

8355

AN:

30302

American (AMR)

AF:

0.355

AC:

14996

AN:

42216

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

10611

AN:

25178

East Asian (EAS)

AF:

0.374

AC:

13736

AN:

36762

South Asian (SAS)

AF:

0.438

AC:

36141

AN:

82518

European-Finnish (FIN)

AF:

0.610

AC:

30688

AN:

50320

Middle Eastern (MID)

AF:

0.410

AC:

2279

AN:

5562

European-Non Finnish (NFE)

AF:

0.419

AC:

459715

AN:

1096756

Other (OTH)

AF:

0.409

AC:

24126

AN:

58974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

14730

29460

44189

58919

73649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14080

28160

42240

56320

70400

<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:

0.388

AC:

58848

AN:

151716

Hom.:

12126

Cov.:

AF XY:

0.399

AC XY:

29578

AN XY:

74146

show subpopulations

African (AFR)

AF:

0.275

AC:

11406

AN:

41444

American (AMR)

AF:

0.376

AC:

5749

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

1386

AN:

3460

East Asian (EAS)

AF:

0.380

AC:

1942

AN:

5106

South Asian (SAS)

AF:

0.421

AC:

2026

AN:

4808

European-Finnish (FIN)

AF:

0.634

AC:

6673

AN:

10522

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.419

AC:

28406

AN:

67792

Other (OTH)

AF:

0.378

AC:

798

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1761

3523

5284

7046

8807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.380

Hom.:

3471

Bravo

AF:

0.362

Asia WGS

AF:

0.383

AC:

1326

AN:

3462

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Hydrocephalus, nonsyndromic, autosomal recessive 1 (1)

Spinocerebellar ataxia type 40 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

-0.13

PromoterAI

0.023

Neutral

(source)

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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