rs941764

Variant names:

• chr14-91374725-A-G
• rs941764
• NM_001080414.4:c.271-15014T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080414.4(CCDC88C):​c.271-15014T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,132 control chromosomes in the GnomAD database, including 17,958 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (17958 hom., cov: 33)
• Consequence: CCDC88C NM_001080414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 84 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4	c.271-15014T>C		intron_variant	Intron 3 of 29	ENST00000389857.11	NP_001073883.2
CCDC88C	NR_189158.1	n.401-15014T>C		intron_variant	Intron 3 of 30
CCDC88C	NR_189159.1	n.401-15014T>C		intron_variant	Intron 3 of 30
CCDC88C	XM_011536796.3	c.163-15014T>C		intron_variant	Intron 3 of 29		XP_011535098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11	c.271-15014T>C		intron_variant	Intron 3 of 29	5	NM_001080414.4	ENSP00000374507.6
CCDC88C	ENST00000553437.1	n.101-15014T>C		intron_variant	Intron 1 of 3	2
CCDC88C	ENST00000554872.5	n.211-15014T>C		intron_variant	Intron 2 of 6	4

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68701 AN: 152012 Hom.: 17919 Cov.: 33

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.434

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.452 AC: 68783 AN: 152132 Hom.: 17958 Cov.: 33 AF XY: 0.449 AC XY: 33426 AN XY: 74376

African (AFR) AF: 0.724 AC: 30043 AN: 41490

American (AMR) AF: 0.466 AC: 7120 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3472

East Asian (EAS) AF: 0.134 AC: 692 AN: 5180

South Asian (SAS) AF: 0.278 AC: 1342 AN: 4826

European-Finnish (FIN) AF: 0.344 AC: 3648 AN: 10592

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23270 AN: 67972

Other (OTH) AF: 0.429 AC: 908 AN: 2116

Alfa AF: 0.384 Hom.: 39269

Bravo AF: 0.476

Asia WGS AF: 0.272 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.56
PhyloP100		0.10
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs941764; hg19: chr14-91841069;