chr14-91371904-G-A

Position:

• chr14-91371904-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080414.4(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 NM_001080414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.81

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC88C	NM_001080414.4	c.271-12193C>T		intron_variant		ENST00000389857.11	NP_001073883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11	c.271-12193C>T		intron_variant		5	NM_001080414.4	ENSP00000374507.6
CCDC88C	ENST00000553437.1	n.101-12193C>T		intron_variant		2
CCDC88C	ENST00000554872.5	n.211-12193C>T		intron_variant		4

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

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0495

Gnomad4 ASJ AF: 0.0600

Gnomad4 EAS AF: 0.00561

Gnomad4 SAS AF: 0.0617

Gnomad4 FIN AF: 0.0257

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0677 Hom.: 56

Bravo AF: 0.0872

Asia WGS AF: 0.0470 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.029
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs17127296; hg19: chr14-91838248;