rs1970911

Variant names:

• chr14-91307150-G-A
• rs1970911
• NM_001080414.4:c.3083C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-91307150-G-A
• chr14-91307150-G-C

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.3083C>T​(p.Ala1028Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,613,634 control chromosomes in the GnomAD database, including 16,496 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1028A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.14 (1510 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14986 hom.)
• Consequence: CCDC88C NM_001080414.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.348
• Publications: 23 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 (MetaRNN=0.0038718283).
• BP6: Variant 14-91307150-G-A is Benign according to our data. Variant chr14-91307150-G-A is described in ClinVar as Benign. ClinVar VariationId is 158099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 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.3083C>T	p.Ala1028Val	missense	Exon 18 of 30	NP_001073883.2	Q9P219-1
	CCDC88C	NR_189158.1		n.3213C>T		non_coding_transcript_exon	Exon 18 of 31
	CCDC88C	NR_189159.1		n.3213C>T		non_coding_transcript_exon	Exon 18 of 31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	ENST00000389857.11	TSL:5 MANE Select	c.3083C>T	p.Ala1028Val	missense	Exon 18 of 30	ENSP00000374507.6	Q9P219-1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21196 AN: 152006 Hom.: 1509 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.160 AC: 39826 AN: 248940 AF XY: 0.161

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.229

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.138 AC: 202394 AN: 1461508 Hom.: 14986 Cov.: 33 AF XY: 0.141 AC XY: 102607 AN XY: 727046

African (AFR) AF: 0.116 AC: 3899 AN: 33476

American (AMR) AF: 0.179 AC: 8022 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3850 AN: 26128

East Asian (EAS) AF: 0.238 AC: 9428 AN: 39694

South Asian (SAS) AF: 0.226 AC: 19489 AN: 86248

European-Finnish (FIN) AF: 0.169 AC: 9006 AN: 53324

Middle Eastern (MID) AF: 0.109 AC: 627 AN: 5764

European-Non Finnish (NFE) AF: 0.125 AC: 139474 AN: 1111792

Other (OTH) AF: 0.142 AC: 8599 AN: 60370

GnomAD4 genome AF: 0.139 AC: 21218 AN: 152126 Hom.: 1510 Cov.: 32 AF XY: 0.146 AC XY: 10840 AN XY: 74370

African (AFR) AF: 0.117 AC: 4858 AN: 41494

American (AMR) AF: 0.176 AC: 2694 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1203 AN: 5160

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4816

European-Finnish (FIN) AF: 0.162 AC: 1717 AN: 10592

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8742 AN: 67992

Other (OTH) AF: 0.146 AC: 308 AN: 2112

Alfa AF: 0.135 Hom.: 5748

Bravo AF: 0.140

TwinsUK AF: 0.120 AC: 445

ALSPAC AF: 0.119 AC: 457

ESP6500AA AF: 0.112 AC: 430

ESP6500EA AF: 0.127 AC: 1051

ExAC AF: 0.159 AC: 19208

Asia WGS AF: 0.203 AC: 704 AN: 3478

EpiCase AF: 0.122

EpiControl AF: 0.123

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
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.17
DANN	Benign	0.78
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.70	N
PhyloP100		-0.35
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.012
Sift	Benign	0.34	T
Sift4G	Benign	0.29	T
Polyphen		0.0040	B
Vest4		0.015
MPC		0.13
ClinPred		0.00058	T
GERP RS		-4.9
Varity_R		0.028
gMVP		0.12
Mutation Taster		=100/0	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: rs1970911; hg19: chr14-91773494; COSMIC: COSV66236673;