Genetic Variant CCDC50:c.50-86delT (chr3-191356994-AT-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_178335.3(CCDC50):c.50-86delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0816 in 791,716 control chromosomes in the GnomAD database, including 3,271 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.078 ( 531 hom., cov: 31)

Exomes 𝑓: 0.082 ( 2740 hom. )

Consequence

CCDC50
NM_178335.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.63

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 3-191356994-AT-A is Benign according to our data. Variant chr3-191356994-AT-A is described in ClinVar as [Benign]. Clinvar id is 1235084.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3 link	c.50-86delT	intron_variant	Intron 1 of 11	ENST00000392455.9	NP_848018.1	Q8IVM0-2
CCDC50	NM_174908.4 link	c.50-86delT	intron_variant	Intron 1 of 10		NP_777568.1	Q8IVM0-1
CCDC50	XM_011512460.2 link	c.50-86delT	intron_variant	Intron 1 of 7		XP_011510762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 link	c.50-93delT		intron_variant	Intron 1 of 11	1	NM_178335.3	ENSP00000376249.4		Q8IVM0-2
CCDC50	ENST00000392456.4 link	c.50-93delT		intron_variant	Intron 1 of 10	1		ENSP00000376250.4		Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.0781

AC:

11820

AN:

151324

Hom.:

528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0527

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.0778

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.0873

Gnomad FIN

AF:

0.0609

Gnomad MID

AF:

0.124

Gnomad NFE

AF:

0.0816

Gnomad OTH

AF:

0.0880

GnomAD4 exome

AF:

0.0824

AC:

52745

AN:

640276

Hom.:

2740

AF XY:

0.0824

AC XY:

28329

AN XY:

343652

show subpopulations

Gnomad4 AFR exome

AF:

0.0449

AC:

720

AN:

16048

Gnomad4 AMR exome

AF:

0.0898

AC:

3122

AN:

34750

Gnomad4 ASJ exome

AF:

0.108

AC:

2210

AN:

20402

Gnomad4 EAS exome

AF:

0.196

AC:

6337

AN:

32304

Gnomad4 SAS exome

AF:

0.0832

AC:

5299

AN:

63666

Gnomad4 FIN exome

AF:

0.0604

AC:

2733

AN:

45220

Gnomad4 NFE exome

AF:

0.0739

AC:

28869

AN:

390570

Gnomad4 Remaining exome

AF:

0.0928

AC:

3080

AN:

33172

Heterozygous variant carriers

2330

4660

6991

9321

11651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.0782

AC:

11842

AN:

151440

Hom.:

531

Cov.:

AF XY:

0.0801

AC XY:

5926

AN XY:

73994

show subpopulations

Gnomad4 AFR

AF:

0.0529

AC:

0.052912

AN:

0.052912

Gnomad4 AMR

AF:

0.0779

AC:

0.0778538

AN:

0.0778538

Gnomad4 ASJ

AF:

0.102

AC:

0.102364

AN:

0.102364

Gnomad4 EAS

AF:

0.245

AC:

0.244866

AN:

0.244866

Gnomad4 SAS

AF:

0.0869

AC:

0.0869112

AN:

0.0869112

Gnomad4 FIN

AF:

0.0609

AC:

0.0608944

AN:

0.0608944

Gnomad4 NFE

AF:

0.0817

AC:

0.081654

AN:

0.081654

Gnomad4 OTH

AF:

0.0928

AC:

0.0927688

AN:

0.0927688

Heterozygous variant carriers

555

1111

1666

2222

2777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.0332

Hom.:

Bravo

AF:

0.0793

Asia WGS

AF:

0.199

AC:

690

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 21, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over