chr3-191357084-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.50-4C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,596,420 control chromosomes in the GnomAD database, including 256,916 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 34148 hom., cov: 31)

Exomes 𝑓: 0.54 ( 222768 hom. )

Consequence

CCDC50
NM_178335.3 splice_region, intron

Scores

Splicing: ADA: 0.00008616

Clinical Significance

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

Conservation

PhyloP100: -0.666

Publications

20 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
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal dominant nonsyndromic hearing loss 44
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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=-0.79).

BP6

Variant 3-191357084-C-G is Benign according to our data. Variant chr3-191357084-C-G is described in ClinVar as Benign. ClinVar VariationId is 48155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178335.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC50	NM_178335.3	MANE Select	c.50-4C>G		splice_region intron	N/A	NP_848018.1	Q8IVM0-2
	CCDC50	NM_174908.4		c.50-4C>G		splice_region intron	N/A	NP_777568.1	Q8IVM0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC50	ENST00000392455.9	TSL:1 MANE Select	c.50-4C>G	splice_region intron	N/A	ENSP00000376249.4	Q8IVM0-2
CCDC50	ENST00000392456.4	TSL:1	c.50-4C>G	splice_region intron	N/A	ENSP00000376250.4	Q8IVM0-1
CCDC50	ENST00000899243.1		c.50-4C>G	splice_region intron	N/A	ENSP00000569302.1

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98902

AN:

151914

Hom.:

34096

Cov.:

show subpopulations

Gnomad AFR

AF:

0.863

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.681

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.919

Gnomad SAS

AF:

0.694

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.605

GnomAD2 exomes

AF:

0.628

AC:

157546

AN:

250812

AF XY:

0.616

show subpopulations

Gnomad AFR exome

AF:

0.869

Gnomad AMR exome

AF:

0.755

Gnomad ASJ exome

AF:

0.551

Gnomad EAS exome

AF:

0.932

Gnomad FIN exome

AF:

0.559

Gnomad NFE exome

AF:

0.514

Gnomad OTH exome

AF:

0.579

GnomAD4 exome

AF:

0.545

AC:

786813

AN:

1444388

Hom.:

222768

Cov.:

AF XY:

0.547

AC XY:

393710

AN XY:

719742

show subpopulations

African (AFR)

AF:

0.871

AC:

28707

AN:

32976

American (AMR)

AF:

0.748

AC:

33401

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.549

AC:

14285

AN:

26036

East Asian (EAS)

AF:

0.898

AC:

35566

AN:

39622

South Asian (SAS)

AF:

0.680

AC:

58384

AN:

85904

European-Finnish (FIN)

AF:

0.553

AC:

29511

AN:

53328

Middle Eastern (MID)

AF:

0.518

AC:

2975

AN:

5746

European-Non Finnish (NFE)

AF:

0.502

AC:

550086

AN:

1096406

Other (OTH)

AF:

0.568

AC:

33898

AN:

59694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

15808

31616

47423

63231

79039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16120

32240

48360

64480

80600

<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:

0.651

AC:

99011

AN:

152032

Hom.:

34148

Cov.:

AF XY:

0.659

AC XY:

48939

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.863

AC:

35831

AN:

41518

American (AMR)

AF:

0.682

AC:

10411

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

1890

AN:

3468

East Asian (EAS)

AF:

0.919

AC:

4767

AN:

5186

South Asian (SAS)

AF:

0.694

AC:

3344

AN:

4816

European-Finnish (FIN)

AF:

0.566

AC:

5942

AN:

10506

Middle Eastern (MID)

AF:

0.619

AC:

182

AN:

294

European-Non Finnish (NFE)

AF:

0.516

AC:

35052

AN:

67958

Other (OTH)

AF:

0.604

AC:

1275

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

1610

3219

4829

6438

8048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.551

Hom.:

7798

Bravo

AF:

0.670

Asia WGS

AF:

0.803

AC:

2786

AN:

3476

EpiCase

AF:

0.512

EpiControl

AF:

0.509

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Autosomal dominant nonsyndromic hearing loss 44 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.1

(source)

DANN

Benign

0.52

PhyloP100

-0.67

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

dbscSNV1_ADA

Benign

0.000086

dbscSNV1_RF

Benign

0.032

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over