chr14-91417623-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080414.4(CCDC88C):​c.60+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,580,304 control chromosomes in the GnomAD database, including 140,642 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12126 hom., cov: 31)
Exomes 𝑓: 0.42 ( 128516 hom. )

Consequence

CCDC88C
NM_001080414.4 splice_region, intron

Scores

2
Splicing: ADA: 0.00003065
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.126
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 14-91417623-G-T is Benign according to our data. Variant chr14-91417623-G-T is described in ClinVar as [Benign]. Clinvar id is 158120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-91417623-G-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC88CNM_001080414.4 linkuse as main transcriptc.60+8C>A splice_region_variant, intron_variant ENST00000389857.11 NP_001073883.2 Q9P219-1B4DZB8
CCDC88CXM_047431419.1 linkuse as main transcriptc.60+8C>A splice_region_variant, intron_variant
CCDC88CXM_005267691.6 linkuse as main transcriptc.60+8C>A splice_region_variant, intron_variant
CCDC88CXM_011536796.3 linkuse as main transcriptc.-293C>A upstream_gene_variant XP_011535098.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC88CENST00000389857.11 linkuse as main transcriptc.60+8C>A splice_region_variant, intron_variant 5 NM_001080414.4 ENSP00000374507.6 Q9P219-1
CCDC88CENST00000553403.1 linkuse as main transcriptc.60+8C>A splice_region_variant, intron_variant 1 ENSP00000451392.1 G3V3S0
CCDC88CENST00000554165.1 linkuse as main transcriptn.48+8C>A splice_region_variant, intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.388
AC:
58836
AN:
151608
Hom.:
12125
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.275
Gnomad AMI
AF:
0.388
Gnomad AMR
AF:
0.377
Gnomad ASJ
AF:
0.401
Gnomad EAS
AF:
0.381
Gnomad SAS
AF:
0.422
Gnomad FIN
AF:
0.634
Gnomad MID
AF:
0.376
Gnomad NFE
AF:
0.419
Gnomad OTH
AF:
0.384
GnomAD3 exomes
AF:
0.415
AC:
84912
AN:
204568
Hom.:
18060
AF XY:
0.419
AC XY:
47651
AN XY:
113842
show subpopulations
Gnomad AFR exome
AF:
0.270
Gnomad AMR exome
AF:
0.351
Gnomad ASJ exome
AF:
0.421
Gnomad EAS exome
AF:
0.363
Gnomad SAS exome
AF:
0.430
Gnomad FIN exome
AF:
0.612
Gnomad NFE exome
AF:
0.413
Gnomad OTH exome
AF:
0.415
GnomAD4 exome
AF:
0.420
AC:
600647
AN:
1428588
Hom.:
128516
Cov.:
31
AF XY:
0.422
AC XY:
299283
AN XY:
709930
show subpopulations
Gnomad4 AFR exome
AF:
0.276
Gnomad4 AMR exome
AF:
0.355
Gnomad4 ASJ exome
AF:
0.421
Gnomad4 EAS exome
AF:
0.374
Gnomad4 SAS exome
AF:
0.438
Gnomad4 FIN exome
AF:
0.610
Gnomad4 NFE exome
AF:
0.419
Gnomad4 OTH exome
AF:
0.409
GnomAD4 genome
AF:
0.388
AC:
58848
AN:
151716
Hom.:
12126
Cov.:
31
AF XY:
0.399
AC XY:
29578
AN XY:
74146
show subpopulations
Gnomad4 AFR
AF:
0.275
Gnomad4 AMR
AF:
0.376
Gnomad4 ASJ
AF:
0.401
Gnomad4 EAS
AF:
0.380
Gnomad4 SAS
AF:
0.421
Gnomad4 FIN
AF:
0.634
Gnomad4 NFE
AF:
0.419
Gnomad4 OTH
AF:
0.378
Alfa
AF:
0.380
Hom.:
3471
Bravo
AF:
0.362
Asia WGS
AF:
0.383
AC:
1326
AN:
3462

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 10, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoApr 08, 2013- -
Spinocerebellar ataxia type 40 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 14, 2021- -
Hydrocephalus, nonsyndromic, autosomal recessive 1 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 14, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
CADD
Benign
12
DANN
Benign
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000031
dbscSNV1_RF
Benign
0.0020
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3742654; hg19: chr14-91883967; COSMIC: COSV66232184; COSMIC: COSV66232184; API