rs211043

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178335.3(CCDC50):c.1242+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,601,236 control chromosomes in the GnomAD database, including 198,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27048 hom., cov: 32)

Exomes 𝑓: 0.48 ( 171058 hom. )

Consequence

CCDC50
NM_178335.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.478

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 3-191380942-G-A is Benign according to our data. Variant chr3-191380942-G-A is described in ClinVar as [Benign]. Clinvar id is 48150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-191380942-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3 link	c.1242+10G>A		intron_variant	Intron 9 of 11	ENST00000392455.9	NP_848018.1	Q8IVM0-2
CCDC50	NM_174908.4 link	c.714+10G>A		intron_variant	Intron 8 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.1242+10G>A		intron_variant	Intron 9 of 11	1	NM_178335.3	ENSP00000376249.4		Q8IVM0-2
CCDC50	ENST00000392456.4 link	c.714+10G>A		intron_variant	Intron 8 of 10	1		ENSP00000376250.4		Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87672

AN:

151792

Hom.:

26994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.806

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.666

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.546

GnomAD3 exomes

AF:

0.534

AC:

127772

AN:

239112

Hom.:

35125

AF XY:

0.522

AC XY:

67586

AN XY:

129522

show subpopulations

Gnomad AFR exome

AF:

0.809

Gnomad AMR exome

AF:

0.627

Gnomad ASJ exome

AF:

0.506

Gnomad EAS exome

AF:

0.684

Gnomad SAS exome

AF:

0.518

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.468

Gnomad OTH exome

AF:

0.508

GnomAD4 exome

AF:

0.481

AC:

696616

AN:

1449326

Hom.:

171058

Cov.:

AF XY:

0.480

AC XY:

345885

AN XY:

720928

show subpopulations

Gnomad4 AFR exome

AF:

0.813

Gnomad4 AMR exome

AF:

0.619

Gnomad4 ASJ exome

AF:

0.504

Gnomad4 EAS exome

AF:

0.645

Gnomad4 SAS exome

AF:

0.518

Gnomad4 FIN exome

AF:

0.444

Gnomad4 NFE exome

AF:

0.457

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.578

AC:

87781

AN:

151910

Hom.:

27048

Cov.:

AF XY:

0.578

AC XY:

42880

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.806

Gnomad4 AMR

AF:

0.566

Gnomad4 ASJ

AF:

0.505

Gnomad4 EAS

AF:

0.665

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.444

Gnomad4 NFE

AF:

0.467

Gnomad4 OTH

AF:

0.544

Alfa

AF:

0.540

Hom.:

6835

Bravo

AF:

0.599

Asia WGS

AF:

0.626

AC:

2171

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

1242+10G>A in Intron 09 of CCDC50: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence and has been identified in 46.1% (3234/7016) of European American chromos omes from a broad population by the NHLBI Exome Sequencing Project (http://evs.g s.washington.edu/EVS; dbSNP rs211043). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

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

-0.77

CADD

Benign

9.8

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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