rs17127255

Variant names:

• chr14-91338035-G-A
• rs17127255
• NM_001080414.4:c.1020C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-91338035-G-A
• chr14-91338035-G-C

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.1020C>T​(p.His340His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,613,004 control chromosomes in the GnomAD database, including 529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (291 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (238 hom.)
• Consequence: CCDC88C NM_001080414.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.860
• Publications: 3 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=-0.8).
• BP6: Variant 14-91338035-G-A is Benign according to our data. Variant chr14-91338035-G-A is described in ClinVar as Benign. ClinVar VariationId is 158089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.86 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 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.1020C>T	p.His340His	synonymous	Exon 10 of 30	NP_001073883.2	Q9P219-1
	CCDC88C	NR_189158.1		n.1150C>T		non_coding_transcript_exon	Exon 10 of 31
	CCDC88C	NR_189159.1		n.1150C>T		non_coding_transcript_exon	Exon 10 of 31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	ENST00000389857.11	TSL:5 MANE Select	c.1020C>T	p.His340His	synonymous	Exon 10 of 30	ENSP00000374507.6	Q9P219-1
	CCDC88C	ENST00000554051.1	TSL:3	n.*19C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4863 AN: 152168 Hom.: 290 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0253

GnomAD2 exomes AF: 0.00835 AC: 2074 AN: 248502 AF XY: 0.00643

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.00521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00340

Gnomad FIN exome AF: 0.0000955

Gnomad NFE exome AF: 0.000443

Gnomad OTH exome AF: 0.00380

GnomAD4 exome AF: 0.00329 AC: 4808 AN: 1460718 Hom.: 238 Cov.: 32 AF XY: 0.00283 AC XY: 2057 AN XY: 726734

African (AFR) AF: 0.110 AC: 3699 AN: 33476

American (AMR) AF: 0.00606 AC: 271 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00202 AC: 80 AN: 39700

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86258

European-Finnish (FIN) AF: 0.000114 AC: 6 AN: 52430

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5766

European-Non Finnish (NFE) AF: 0.000281 AC: 312 AN: 1111864

Other (OTH) AF: 0.00663 AC: 400 AN: 60366

GnomAD4 genome AF: 0.0320 AC: 4868 AN: 152286 Hom.: 291 Cov.: 33 AF XY: 0.0311 AC XY: 2314 AN XY: 74450

African (AFR) AF: 0.111 AC: 4600 AN: 41530

American (AMR) AF: 0.0102 AC: 156 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68022

Other (OTH) AF: 0.0250 AC: 53 AN: 2116

Alfa AF: 0.0146 Hom.: 78

Bravo AF: 0.0371

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000593

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	-0.80
CADD	Benign	0.11
DANN	Benign	0.90
PhyloP100		-0.86
Mutation Taster		=97/3	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: rs17127255; hg19: chr14-91804379;