rs2028572

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.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

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=-0.94).

BP6

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

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

GnomAD3 exomes

AF:

0.428

AC:

107004

AN:

250000

Hom.:

23677

AF XY:

0.416

AC XY:

56172

AN XY:

135096

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 SAS exome

AF:

0.353

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

Gnomad4 AFR exome

AF:

0.684

Gnomad4 AMR exome

AF:

0.496

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.410

Gnomad4 SAS exome

AF:

0.360

Gnomad4 FIN exome

AF:

0.368

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.483

AC:

73456

AN:

151942

Hom.:

18933

Cov.:

AF XY:

0.482

AC XY:

35762

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.683

Gnomad4 AMR

AF:

0.473

Gnomad4 ASJ

AF:

0.462

Gnomad4 EAS

AF:

0.455

Gnomad4 SAS

AF:

0.352

Gnomad4 FIN

AF:

0.374

Gnomad4 NFE

AF:

0.398

Gnomad4 OTH

AF:

0.458

Alfa

AF:

0.418

Hom.:

27862

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

DANN

Benign

0.35

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