rs146511344

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_178335.3(CCDC50):c.1203A>G(p.Lys401Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,612,942 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 7 hom. )

Consequence

CCDC50
NM_178335.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.455

Publications

1 publications found

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]

CCDC50 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 44
Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CCDC50 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-191380893-A-G is Benign according to our data. Variant chr3-191380893-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 162861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.455 with no splicing effect.

BS2

High AC in GnomAd4 at 239 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3 link	c.1203A>G	p.Lys401Lys	synonymous_variant	Exon 9 of 12	ENST00000392455.9	NP_848018.1	Q8IVM0-2
CCDC50	NM_174908.4 link	c.675A>G	p.Lys225Lys	synonymous_variant	Exon 8 of 11		NP_777568.1	Q8IVM0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 link	c.1203A>G	p.Lys401Lys	synonymous_variant	Exon 9 of 12	1	NM_178335.3	ENSP00000376249.4		Q8IVM0-2
CCDC50	ENST00000392456.4 link	c.675A>G	p.Lys225Lys	synonymous_variant	Exon 8 of 11	1		ENSP00000376250.4		Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

238

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00260

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00171

AC:

427

AN:

250150

AF XY:

0.00180

show subpopulations

Gnomad AFR exome

AF:

0.000496

Gnomad AMR exome

AF:

0.000959

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.000602

Gnomad NFE exome

AF:

0.00287

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00225

AC:

3286

AN:

1460694

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

1587

AN XY:

726640

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33432

American (AMR)

AF:

0.00110

AC:

AN:

44608

Ashkenazi Jewish (ASJ)

AF:

0.0000767

AC:

AN:

26090

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39642

South Asian (SAS)

AF:

0.00129

AC:

111

AN:

86216

European-Finnish (FIN)

AF:

0.000581

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00266

AC:

2961

AN:

1111226

Other (OTH)

AF:

0.00197

AC:

119

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

174

348

523

697

871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152248

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41562

American (AMR)

AF:

0.00262

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000376

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00260

AC:

177

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.00155

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00238

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 05, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CCDC50: BP4, BP7 -

not specified

Benign:2

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Lys401Lys in Exon 09 of CCDC50: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.3% (21/7018) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs146511344). -

Jul 31, 2017

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CCDC50-related disorder

Benign:1

Jan 06, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.3

(source)

DANN

Benign

0.44

PhyloP100

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over