Genetic Variant CCDC50:c.1243-888A>G (chr3-191381858-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178335.3(CCDC50):c.1243-888A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,910 control chromosomes in the GnomAD database, including 27,035 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 27035 hom., cov: 31)

Consequence

CCDC50
NM_178335.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.195

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.1243-888A>G		intron_variant	Intron 9 of 11	ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4 link	c.715-888A>G		intron_variant	Intron 8 of 10		NP_777568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 link	c.1243-888A>G		intron_variant	Intron 9 of 11	1	NM_178335.3	ENSP00000376249.4
CCDC50	ENST00000392456.4 link	c.715-888A>G		intron_variant	Intron 8 of 10	1		ENSP00000376250.4

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87659

AN:

151792

Hom.:

26981

Cov.:

show subpopulations

Gnomad AFR

AF:

0.806

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.504

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

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.578

AC:

87768

AN:

151910

Hom.:

27035

Cov.:

AF XY:

0.578

AC XY:

42879

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.806

AC:

33422

AN:

41458

American (AMR)

AF:

0.567

AC:

8640

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

1750

AN:

3472

East Asian (EAS)

AF:

0.665

AC:

3428

AN:

5156

South Asian (SAS)

AF:

0.522

AC:

2510

AN:

4812

European-Finnish (FIN)

AF:

0.444

AC:

4679

AN:

10530

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.467

AC:

31712

AN:

67918

Other (OTH)

AF:

0.544

AC:

1147

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1733

3466

5199

6932

8665

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:

0.540

Hom.:

3029

Bravo

AF:

0.599

Asia WGS

AF:

0.626

AC:

2171

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.6

(source)

DANN

Benign

0.56

PhyloP100

-0.20

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over