rs2028573

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_178335.3(CCDC50):c.678A>G(p.Lys226Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 1,613,458 control chromosomes in the GnomAD database, including 12,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4038 hom., cov: 32)

Exomes 𝑓: 0.090 ( 8790 hom. )

Consequence

CCDC50
NM_178335.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.614

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 3-191375291-A-G is Benign according to our data. Variant chr3-191375291-A-G is described in ClinVar as [Benign]. Clinvar id is 48157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-191375291-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.614 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3 link	c.678A>G	p.Lys226Lys	synonymous_variant	Exon 6 of 12	ENST00000392455.9	NP_848018.1	Q8IVM0-2
CCDC50	XM_011512460.2 link	c.678A>G	p.Lys226Lys	synonymous_variant	Exon 6 of 8		XP_011510762.1
CCDC50	NM_174908.4 link	c.449-4868A>G		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.678A>G	p.Lys226Lys	synonymous_variant	Exon 6 of 12	1	NM_178335.3	ENSP00000376249.4		Q8IVM0-2
CCDC50	ENST00000392456.4 link	c.449-4868A>G		intron_variant	Intron 5 of 10	1		ENSP00000376250.4		Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27071

AN:

152014

Hom.:

4033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.0930

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.0393

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.0727

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.123

AC:

30769

AN:

249834

Hom.:

2848

AF XY:

0.114

AC XY:

15423

AN XY:

135028

show subpopulations

Gnomad AFR exome

AF:

0.407

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.0958

Gnomad EAS exome

AF:

0.209

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.0444

Gnomad NFE exome

AF:

0.0733

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.0898

AC:

131291

AN:

1461326

Hom.:

8790

Cov.:

AF XY:

0.0889

AC XY:

64594

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.416

Gnomad4 AMR exome

AF:

0.170

Gnomad4 ASJ exome

AF:

0.0941

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0430

Gnomad4 NFE exome

AF:

0.0711

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.178

AC:

27097

AN:

152132

Hom.:

4038

Cov.:

AF XY:

0.174

AC XY:

12974

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.0930

Gnomad4 EAS

AF:

0.213

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.0393

Gnomad4 NFE

AF:

0.0726

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.0971

Hom.:

1896

Bravo

AF:

0.196

Asia WGS

AF:

0.163

AC:

567

AN:

3478

EpiCase

AF:

0.0763

EpiControl

AF:

0.0768

ClinVar

Significance: Benign

Submissions summary: Benign:5

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Lys226Lys 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 39.2% (1467/3738) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2028573). -

not provided

Benign:2

Feb 02, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.38

DANN

Benign

0.36

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