3-191380750-C-G

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.1137+19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 1,611,598 control chromosomes in the GnomAD database, including 5,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 482 hom., cov: 32)

Exomes 𝑓: 0.063 ( 4642 hom. )

Consequence

CCDC50
NM_178335.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.259

Publications

6 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=-0.81).

BP6

Variant 3-191380750-C-G is Benign according to our data. Variant chr3-191380750-C-G is described in ClinVar as Benign. ClinVar VariationId is 262930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3 link	c.1137+19C>G		intron_variant	Intron 8 of 11	ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4 link	c.609+19C>G		intron_variant	Intron 7 of 10		NP_777568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 link	c.1137+19C>G		intron_variant	Intron 8 of 11	1	NM_178335.3	ENSP00000376249.4
CCDC50	ENST00000392456.4 link	c.609+19C>G		intron_variant	Intron 7 of 10	1		ENSP00000376250.4

Frequencies

GnomAD3 genomes

AF:

0.0593

AC:

9020

AN:

151994

Hom.:

481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00980

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0483

Gnomad OTH

AF:

0.0523

GnomAD2 exomes

AF:

0.0910

AC:

22680

AN:

249274

AF XY:

0.0927

show subpopulations

Gnomad AFR exome

AF:

0.00964

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.0452

Gnomad EAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.0481

Gnomad OTH exome

AF:

0.0693

GnomAD4 exome

AF:

0.0633

AC:

92385

AN:

1459486

Hom.:

4642

Cov.:

AF XY:

0.0664

AC XY:

48192

AN XY:

726058

show subpopulations

African (AFR)

AF:

0.00940

AC:

314

AN:

33418

American (AMR)

AF:

0.126

AC:

5611

AN:

44508

Ashkenazi Jewish (ASJ)

AF:

0.0446

AC:

1163

AN:

26084

East Asian (EAS)

AF:

0.247

AC:

9798

AN:

39590

South Asian (SAS)

AF:

0.161

AC:

13900

AN:

86108

European-Finnish (FIN)

AF:

0.110

AC:

5855

AN:

53310

Middle Eastern (MID)

AF:

0.0549

AC:

316

AN:

5760

European-Non Finnish (NFE)

AF:

0.0463

AC:

51439

AN:

1110450

Other (OTH)

AF:

0.0662

AC:

3989

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

4254

8508

12762

17016

21270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2154

4308

6462

8616

10770

<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:

0.0594

AC:

9033

AN:

152112

Hom.:

482

Cov.:

AF XY:

0.0672

AC XY:

4999

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00980

AC:

407

AN:

41530

American (AMR)

AF:

0.111

AC:

1690

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

136

AN:

3468

East Asian (EAS)

AF:

0.251

AC:

1298

AN:

5174

South Asian (SAS)

AF:

0.171

AC:

823

AN:

4814

European-Finnish (FIN)

AF:

0.119

AC:

1265

AN:

10598

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0483

AC:

3281

AN:

67980

Other (OTH)

AF:

0.0536

AC:

113

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

398

797

1195

1594

1992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0538

Hom.:

Bravo

AF:

0.0551

Asia WGS

AF:

0.178

AC:

618

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 16, 2018

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.

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.81

CADD

Benign

(source)

DANN

Benign

0.49

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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