NM_001080414.4:c.3636-14C>T

Variant names:

• chr14-91300084-G-A
• rs112211533
• NM_001080414.4:c.3636-14C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080414.4(CCDC88C):​c.3636-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,604,306 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (62 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (57 hom.)
• Consequence: CCDC88C NM_001080414.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.00600
• Publications: 1 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: 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 14-91300084-G-A is Benign according to our data. Variant chr14-91300084-G-A is described in ClinVar as Benign. ClinVar VariationId is 158109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	NM_001080414.4	MANE Select	c.3636-14C>T		intron	N/A	NP_001073883.2	Q9P219-1
	CCDC88C	NR_189158.1		n.3766-14C>T		intron	N/A
	CCDC88C	NR_189159.1		n.3766-14C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	ENST00000389857.11	TSL:5 MANE Select	c.3636-14C>T		intron	N/A	ENSP00000374507.6	Q9P219-1

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2364 AN: 152258 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00536

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00907

GnomAD2 exomes AF: 0.00381 AC: 876 AN: 230088 AF XY: 0.00284

Gnomad AFR exome AF: 0.0575

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000104

Gnomad NFE exome AF: 0.000173

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00158 AC: 2299 AN: 1451930 Hom.: 57 Cov.: 31 AF XY: 0.00135 AC XY: 976 AN XY: 721404

African (AFR) AF: 0.0552 AC: 1837 AN: 33286

American (AMR) AF: 0.00277 AC: 121 AN: 43646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25866

East Asian (EAS) AF: 0.00 AC: 0 AN: 39372

South Asian (SAS) AF: 0.000142 AC: 12 AN: 84370

European-Finnish (FIN) AF: 0.000117 AC: 6 AN: 51242

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5758

European-Non Finnish (NFE) AF: 0.0000839 AC: 93 AN: 1108374

Other (OTH) AF: 0.00357 AC: 214 AN: 60016

GnomAD4 genome AF: 0.0157 AC: 2393 AN: 152376 Hom.: 62 Cov.: 33 AF XY: 0.0156 AC XY: 1159 AN XY: 74514

African (AFR) AF: 0.0548 AC: 2277 AN: 41578

American (AMR) AF: 0.00536 AC: 82 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68048

Other (OTH) AF: 0.00898 AC: 19 AN: 2116

Alfa AF: 0.00835 Hom.: 4

Bravo AF: 0.0177

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.29
DANN	Benign	0.40
PhyloP100		-0.0060
Mutation Taster		=100/0	polymorphism

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: rs112211533; hg19: chr14-91766428;