rs112741231

Variant names:

• chr14-91303964-C-T
• rs112741231
• NM_001080414.4:c.3372G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001080414.4(CCDC88C):​c.3372G>A​(p.Thr1124Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00429 in 1,602,506 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (104 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (88 hom.)
• Consequence: CCDC88C NM_001080414.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.84
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 14-91303964-C-T is Benign according to our data. Variant chr14-91303964-C-T is described in ClinVar as Benign. ClinVar VariationId is 158107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.065 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.3372G>A	p.Thr1124Thr	synonymous	Exon 20 of 30	NP_001073883.2	Q9P219-1
	CCDC88C	NR_189158.1		n.3502G>A		non_coding_transcript_exon	Exon 20 of 31
	CCDC88C	NR_189159.1		n.3502G>A		non_coding_transcript_exon	Exon 20 of 31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	ENST00000389857.11	TSL:5 MANE Select	c.3372G>A	p.Thr1124Thr	synonymous	Exon 20 of 30	ENSP00000374507.6	Q9P219-1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3046 AN: 152220 Hom.: 98 Cov.: 33

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000955

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00569 AC: 1376 AN: 241776 AF XY: 0.00434

Gnomad AFR exome AF: 0.0689

Gnomad AMR exome AF: 0.00452

Gnomad ASJ exome AF: 0.000300

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00111

Gnomad OTH exome AF: 0.00468

GnomAD4 exome AF: 0.00262 AC: 3801 AN: 1450168 Hom.: 88 Cov.: 33 AF XY: 0.00238 AC XY: 1712 AN XY: 720808

African (AFR) AF: 0.0696 AC: 2325 AN: 33384

American (AMR) AF: 0.00531 AC: 237 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39550

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46194

Middle Eastern (MID) AF: 0.00851 AC: 49 AN: 5756

European-Non Finnish (NFE) AF: 0.000718 AC: 796 AN: 1108300

Other (OTH) AF: 0.00620 AC: 372 AN: 60032

GnomAD4 genome AF: 0.0202 AC: 3072 AN: 152338 Hom.: 104 Cov.: 33 AF XY: 0.0196 AC XY: 1461 AN XY: 74490

African (AFR) AF: 0.0671 AC: 2788 AN: 41566

American (AMR) AF: 0.0117 AC: 179 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000955 AC: 65 AN: 68038

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0147 Hom.: 22

Bravo AF: 0.0230

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00124

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	-0.73
CADD	Benign	0.038
DANN	Benign	0.94
PhyloP100		-4.8
Mutation Taster		=95/5	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: rs112741231; hg19: chr14-91770308;