rs2028572

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_178335.3(CCDC50):c.651T>C(p.His217His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,613,266 control chromosomes in the GnomAD database, including 138,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18933 hom., cov: 32)

Exomes 𝑓: 0.40 ( 119346 hom. )

Consequence

CCDC50
NM_178335.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.02

Publications

28 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 3-191375264-T-C is Benign according to our data. Variant chr3-191375264-T-C is described in ClinVar as Benign. ClinVar VariationId is 48156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3 link	c.651T>C	p.His217His	synonymous_variant	Exon 6 of 12	ENST00000392455.9	NP_848018.1	Q8IVM0-2
CCDC50	XM_011512460.2 link	c.651T>C	p.His217His	synonymous_variant	Exon 6 of 8		XP_011510762.1
CCDC50	NM_174908.4 link	c.449-4895T>C		intron_variant	Intron 5 of 10		NP_777568.1	Q8IVM0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 link	c.651T>C	p.His217His	synonymous_variant	Exon 6 of 12	1	NM_178335.3	ENSP00000376249.4		Q8IVM0-2
CCDC50	ENST00000392456.4 link	c.449-4895T>C		intron_variant	Intron 5 of 10	1		ENSP00000376250.4		Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73370

AN:

151824

Hom.:

18907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.683

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.459

GnomAD2 exomes

AF:

0.428

AC:

107004

AN:

250000

AF XY:

0.416

show subpopulations

Gnomad AFR exome

AF:

0.684

Gnomad AMR exome

AF:

0.497

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.454

Gnomad FIN exome

AF:

0.371

Gnomad NFE exome

AF:

0.395

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.401

AC:

585556

AN:

1461324

Hom.:

119346

Cov.:

AF XY:

0.398

AC XY:

289105

AN XY:

726972

show subpopulations

African (AFR)

AF:

0.684

AC:

22874

AN:

33442

American (AMR)

AF:

0.496

AC:

22133

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

11994

AN:

26116

East Asian (EAS)

AF:

0.410

AC:

16279

AN:

39670

South Asian (SAS)

AF:

0.360

AC:

31016

AN:

86242

European-Finnish (FIN)

AF:

0.368

AC:

19662

AN:

53370

Middle Eastern (MID)

AF:

0.388

AC:

2232

AN:

5760

European-Non Finnish (NFE)

AF:

0.391

AC:

434375

AN:

1111722

Other (OTH)

AF:

0.414

AC:

24991

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

21652

43304

64955

86607

108259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13706

27412

41118

54824

68530

<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:

73456

AN:

151942

Hom.:

18933

Cov.:

AF XY:

0.482

AC XY:

35762

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.683

AC:

28335

AN:

41498

American (AMR)

AF:

0.473

AC:

7206

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

1603

AN:

3470

East Asian (EAS)

AF:

0.455

AC:

2338

AN:

5138

South Asian (SAS)

AF:

0.352

AC:

1692

AN:

4810

European-Finnish (FIN)

AF:

0.374

AC:

3938

AN:

10540

Middle Eastern (MID)

AF:

0.473

AC:

138

AN:

292

European-Non Finnish (NFE)

AF:

0.398

AC:

27001

AN:

67916

Other (OTH)

AF:

0.458

AC:

970

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1865

3730

5594

7459

9324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.435

Hom.:

48662

Bravo

AF:

0.503

Asia WGS

AF:

0.440

AC:

1529

AN:

3478

EpiCase

AF:

0.395

EpiControl

AF:

0.392

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 09, 2017

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. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

His217His in Exon 06 of CCDC50: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 39.5% (2776/7020) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2028572). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal dominant nonsyndromic hearing loss 44

Benign:1

Jul 14, 2021

Genome-Nilou Lab

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

-0.94

CADD

Benign

0.030

(source)

DANN

Benign

0.35

PhyloP100

-3.0

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over