rs17127296

Variant names:

• chr14-91371904-G-A
• rs17127296
• NM_001080414.4:c.271-12193C>T

Variant summary

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

The ENST00000389857.11(CCDC88C):​c.271-12193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 152,180 control chromosomes in the GnomAD database, including 750 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 0.082 (750 hom., cov: 31)
• Consequence: CCDC88C ENST00000389857.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.81
• Publications: 4 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

LOC107984673 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000389857.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	NM_001080414.4	MANE Select	c.271-12193C>T		intron	N/A	NP_001073883.2
	CCDC88C	NR_189158.1		n.401-12193C>T		intron	N/A
	CCDC88C	NR_189159.1		n.401-12193C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	ENST00000389857.11	TSL:5 MANE Select	c.271-12193C>T		intron	N/A	ENSP00000374507.6
	CCDC88C	ENST00000553437.1	TSL:2	n.101-12193C>T		intron	N/A
	CCDC88C	ENST00000554872.5	TSL:4	n.211-12193C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12470 AN: 152062 Hom.: 746 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.00560

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.0257

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0820 AC: 12480 AN: 152180 Hom.: 750 Cov.: 31 AF XY: 0.0794 AC XY: 5905 AN XY: 74408

African (AFR) AF: 0.165 AC: 6853 AN: 41504

American (AMR) AF: 0.0495 AC: 757 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3468

East Asian (EAS) AF: 0.00561 AC: 29 AN: 5166

South Asian (SAS) AF: 0.0617 AC: 298 AN: 4830

European-Finnish (FIN) AF: 0.0257 AC: 273 AN: 10614

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0564 AC: 3835 AN: 67980

Other (OTH) AF: 0.0739 AC: 156 AN: 2112

Alfa AF: 0.0642 Hom.: 74

Bravo AF: 0.0872

Asia WGS AF: 0.0470 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.029
DANN	Benign	0.55
PhyloP100		-5.8
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: rs17127296; hg19: chr14-91838248;