14-91374725-A-G

Position:

• chr14-91374725-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CCDC88C	NM_001080414.4	c.271-15014T>C		intron_variant		ENST00000389857.11	NP_001073883.2
CCDC88C	XM_005267691.6	c.271-15014T>C		intron_variant			XP_005267748.1
CCDC88C	XM_011536796.3	c.163-15014T>C		intron_variant			XP_011535098.1
CCDC88C	XM_047431419.1	c.271-15014T>C		intron_variant			XP_047287375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11	c.271-15014T>C		intron_variant		5	NM_001080414.4	ENSP00000374507	P1
CCDC88C	ENST00000553437.1	n.101-15014T>C		intron_variant, non_coding_transcript_variant		2
CCDC88C	ENST00000554872.5	n.211-15014T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.429

Alfa AF: 0.366 Hom.: 12694

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

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: rs941764; hg19: chr14-91841069;