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GeneBe

rs188384

Variant summary

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

The NM_178335.3(CCDC50):c.50-4C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,596,420 control chromosomes in the GnomAD database, including 256,916 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 34148 hom., cov: 31)
Exomes 𝑓: 0.54 ( 222768 hom. )

Consequence

CCDC50
NM_178335.3 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00008616
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.666
Variant links:
Genes affected
CCDC50 (HGNC:18111): (coiled-coil domain containing 50) This gene encodes a soluble, cytoplasmic, tyrosine-phosphorylated protein with multiple ubiquitin-interacting domains. Mutations in this gene cause nonsyndromic, postlingual, progressive sensorineural DFNA44 hearing loss. In mouse, the protein is expressed in the inner ear during development and postnatal maturation and associates with microtubule-based structures. This protein may also function as a negative regulator of NF-kB signaling and as an effector of epidermal growth factor (EGF)-mediated cell signaling. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

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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=-0.79).
BP6
Variant 3-191357084-C-G is Benign according to our data. Variant chr3-191357084-C-G is described in ClinVar as [Benign]. Clinvar id is 48155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-191357084-C-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCDC50NM_178335.3 linkuse as main transcriptc.50-4C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000392455.9
CCDC50NM_174908.4 linkuse as main transcriptc.50-4C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
CCDC50XM_011512460.2 linkuse as main transcriptc.50-4C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCDC50ENST00000392455.9 linkuse as main transcriptc.50-4C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_178335.3 P3Q8IVM0-2
CCDC50ENST00000392456.4 linkuse as main transcriptc.50-4C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 A1Q8IVM0-1

Frequencies

GnomAD3 genomes
AF:
0.651
AC:
98902
AN:
151914
Hom.:
34096
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.863
Gnomad AMI
AF:
0.349
Gnomad AMR
AF:
0.681
Gnomad ASJ
AF:
0.545
Gnomad EAS
AF:
0.919
Gnomad SAS
AF:
0.694
Gnomad FIN
AF:
0.566
Gnomad MID
AF:
0.604
Gnomad NFE
AF:
0.516
Gnomad OTH
AF:
0.605
GnomAD3 exomes
AF:
0.628
AC:
157546
AN:
250812
Hom.:
52148
AF XY:
0.616
AC XY:
83504
AN XY:
135530
show subpopulations
Gnomad AFR exome
AF:
0.869
Gnomad AMR exome
AF:
0.755
Gnomad ASJ exome
AF:
0.551
Gnomad EAS exome
AF:
0.932
Gnomad SAS exome
AF:
0.681
Gnomad FIN exome
AF:
0.559
Gnomad NFE exome
AF:
0.514
Gnomad OTH exome
AF:
0.579
GnomAD4 exome
AF:
0.545
AC:
786813
AN:
1444388
Hom.:
222768
Cov.:
32
AF XY:
0.547
AC XY:
393710
AN XY:
719742
show subpopulations
Gnomad4 AFR exome
AF:
0.871
Gnomad4 AMR exome
AF:
0.748
Gnomad4 ASJ exome
AF:
0.549
Gnomad4 EAS exome
AF:
0.898
Gnomad4 SAS exome
AF:
0.680
Gnomad4 FIN exome
AF:
0.553
Gnomad4 NFE exome
AF:
0.502
Gnomad4 OTH exome
AF:
0.568
GnomAD4 genome
AF:
0.651
AC:
99011
AN:
152032
Hom.:
34148
Cov.:
31
AF XY:
0.659
AC XY:
48939
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.863
Gnomad4 AMR
AF:
0.682
Gnomad4 ASJ
AF:
0.545
Gnomad4 EAS
AF:
0.919
Gnomad4 SAS
AF:
0.694
Gnomad4 FIN
AF:
0.566
Gnomad4 NFE
AF:
0.516
Gnomad4 OTH
AF:
0.604
Alfa
AF:
0.551
Hom.:
7798
Bravo
AF:
0.670
Asia WGS
AF:
0.803
AC:
2786
AN:
3476
EpiCase
AF:
0.512
EpiControl
AF:
0.509

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxMay 09, 2017This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMay 07, 201250-4C>G in Intron 01 of CCDC50: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce and has been identified in 49.3% (3462/7020) of European American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs188384). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
Autosomal dominant nonsyndromic hearing loss 44 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
-0.79
Cadd
Benign
1.1
Dann
Benign
0.52
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000086
dbscSNV1_RF
Benign
0.032
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

Publications

LitVar

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

Other links and lift over

dbSNP: rs188384; hg19: chr3-191074873; COSMIC: COSV66669473; COSMIC: COSV66669473; API