NM_178335.3:c.1242+10G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178335.3(CCDC50):c.1242+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,601,236 control chromosomes in the GnomAD database, including 198,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27048 hom., cov: 32)

Exomes 𝑓: 0.48 ( 171058 hom. )

Consequence

CCDC50
NM_178335.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.478

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 3-191380942-G-A is Benign according to our data. Variant chr3-191380942-G-A is described in ClinVar as Benign. ClinVar VariationId is 48150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3 link	c.1242+10G>A		intron_variant	Intron 9 of 11	ENST00000392455.9	NP_848018.1	Q8IVM0-2
CCDC50	NM_174908.4 link	c.714+10G>A		intron_variant	Intron 8 of 10		NP_777568.1	Q8IVM0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 link	c.1242+10G>A		intron_variant	Intron 9 of 11	1	NM_178335.3	ENSP00000376249.4		Q8IVM0-2
CCDC50	ENST00000392456.4 link	c.714+10G>A		intron_variant	Intron 8 of 10	1		ENSP00000376250.4		Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87672

AN:

151792

Hom.:

26994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.806

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.666

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.546

GnomAD2 exomes

AF:

0.534

AC:

127772

AN:

239112

AF XY:

0.522

show subpopulations

Gnomad AFR exome

AF:

0.809

Gnomad AMR exome

AF:

0.627

Gnomad ASJ exome

AF:

0.506

Gnomad EAS exome

AF:

0.684

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.468

Gnomad OTH exome

AF:

0.508

GnomAD4 exome

AF:

0.481

AC:

696616

AN:

1449326

Hom.:

171058

Cov.:

AF XY:

0.480

AC XY:

345885

AN XY:

720928

show subpopulations

African (AFR)

AF:

0.813

AC:

26900

AN:

33074

American (AMR)

AF:

0.619

AC:

27258

AN:

44028

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

13093

AN:

25972

East Asian (EAS)

AF:

0.645

AC:

25316

AN:

39248

South Asian (SAS)

AF:

0.518

AC:

44076

AN:

85130

European-Finnish (FIN)

AF:

0.444

AC:

23575

AN:

53052

Middle Eastern (MID)

AF:

0.468

AC:

2684

AN:

5740

European-Non Finnish (NFE)

AF:

0.457

AC:

503814

AN:

1103230

Other (OTH)

AF:

0.500

AC:

29900

AN:

59852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

17130

34260

51391

68521

85651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15310

30620

45930

61240

76550

<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:

0.578

AC:

87781

AN:

151910

Hom.:

27048

Cov.:

AF XY:

0.578

AC XY:

42880

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.806

AC:

33441

AN:

41476

American (AMR)

AF:

0.566

AC:

8635

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1749

AN:

3464

East Asian (EAS)

AF:

0.665

AC:

3429

AN:

5154

South Asian (SAS)

AF:

0.522

AC:

2515

AN:

4820

European-Finnish (FIN)

AF:

0.444

AC:

4671

AN:

10530

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.467

AC:

31709

AN:

67898

Other (OTH)

AF:

0.544

AC:

1150

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1745

3490

5235

6980

8725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.544

Hom.:

7088

Bravo

AF:

0.599

Asia WGS

AF:

0.626

AC:

2171

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

1242+10G>A in Intron 09 of CCDC50: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence and has been identified in 46.1% (3234/7016) of European American chromos omes from a broad population by the NHLBI Exome Sequencing Project (http://evs.g s.washington.edu/EVS; dbSNP rs211043). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal dominant nonsyndromic hearing loss 44

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.8

(source)

DANN

Benign

0.68

PhyloP100

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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