rs4677728

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.908A>G(p.Lys303Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,612,776 control chromosomes in the GnomAD database, including 138,202 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18914 hom., cov: 30)

Exomes 𝑓: 0.40 ( 119288 hom. )

Consequence

CCDC50
NM_178335.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.36

Publications

46 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 (MetaRNN=4.6898535E-6).

BP6

Variant 3-191375521-A-G is Benign according to our data. Variant chr3-191375521-A-G is described in ClinVar as Benign. ClinVar VariationId is 48159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 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.908A>G	p.Lys303Arg	missense	Exon 6 of 12	NP_848018.1	Q8IVM0-2
	CCDC50	NM_174908.4		c.449-4638A>G		intron	N/A	NP_777568.1	Q8IVM0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC50	ENST00000392455.9	TSL:1 MANE Select	c.908A>G	p.Lys303Arg	missense	Exon 6 of 12	ENSP00000376249.4	Q8IVM0-2
CCDC50	ENST00000392456.4	TSL:1	c.449-4638A>G		intron	N/A	ENSP00000376250.4	Q8IVM0-1
CCDC50	ENST00000899243.1		c.908A>G	p.Lys303Arg	missense	Exon 6 of 13	ENSP00000569302.1

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73274

AN:

151674

Hom.:

18888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.683

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.452

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.460

GnomAD2 exomes

AF:

0.427

AC:

106550

AN:

249270

AF XY:

0.415

show subpopulations

Gnomad AFR exome

AF:

0.684

Gnomad AMR exome

AF:

0.496

Gnomad ASJ exome

AF:

0.461

Gnomad EAS exome

AF:

0.454

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.394

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.401

AC:

585360

AN:

1460984

Hom.:

119288

Cov.:

AF XY:

0.398

AC XY:

289003

AN XY:

726788

show subpopulations

African (AFR)

AF:

0.684

AC:

22874

AN:

33448

American (AMR)

AF:

0.495

AC:

22091

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

11987

AN:

26110

East Asian (EAS)

AF:

0.410

AC:

16273

AN:

39662

South Asian (SAS)

AF:

0.360

AC:

30999

AN:

86210

European-Finnish (FIN)

AF:

0.368

AC:

19650

AN:

53338

Middle Eastern (MID)

AF:

0.387

AC:

2230

AN:

5756

European-Non Finnish (NFE)

AF:

0.391

AC:

434272

AN:

1111514

Other (OTH)

AF:

0.414

AC:

24984

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

19590

39180

58770

78360

97950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13702

27404

41106

54808

68510

<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:

0.483

AC:

73360

AN:

151792

Hom.:

18914

Cov.:

AF XY:

0.482

AC XY:

35735

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.683

AC:

28273

AN:

41396

American (AMR)

AF:

0.473

AC:

7201

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

1600

AN:

3468

East Asian (EAS)

AF:

0.455

AC:

2329

AN:

5124

South Asian (SAS)

AF:

0.352

AC:

1683

AN:

4780

European-Finnish (FIN)

AF:

0.373

AC:

3950

AN:

10584

Middle Eastern (MID)

AF:

0.466

AC:

136

AN:

292

European-Non Finnish (NFE)

AF:

0.397

AC:

26988

AN:

67906

Other (OTH)

AF:

0.459

AC:

969

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1775

3550

5325

7100

8875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.428

Hom.:

50733

Bravo

AF:

0.503

TwinsUK

AF:

0.384

AC:

1425

ALSPAC

AF:

0.398

AC:

1532

ESP6500AA

AF:

0.671

AC:

2953

ESP6500EA

AF:

0.395

AC:

3398

ExAC

AF:

0.427

AC:

51792

Asia WGS

AF:

0.440

AC:

1528

AN:

3478

EpiCase

AF:

0.395

EpiControl

AF:

0.392

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Autosomal dominant nonsyndromic hearing loss 44 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.87

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0000047

MetaSVM

Benign

-0.95

PhyloP100

1.4

PrimateAI

Benign

0.27

Polyphen

0.11

ClinPred

0.0019

GERP RS

2.3

gMVP

0.013

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over