chr3-191357084-C-G

Position:

chr3-191357084-C-G

Variant summary

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

The NM_178335.3(CCDC50):c.50-4C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,596,420 control chromosomes in the GnomAD database, including 256,916 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 34148 hom., cov: 31)

Exomes 𝑓: 0.54 ( 222768 hom. )

Consequence

CCDC50
NM_178335.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008616

Clinical Significance

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

Conservation

PhyloP100: -0.666

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=-0.79).

BP6

Variant 3-191357084-C-G is Benign according to our data. Variant chr3-191357084-C-G is described in ClinVar as [Benign]. Clinvar id is 48155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-191357084-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CCDC50	NM_178335.3 linkuse as main transcript	c.50-4C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4 linkuse as main transcript	c.50-4C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_777568.1
CCDC50	XM_011512460.2 linkuse as main transcript	c.50-4C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_011510762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 linkuse as main transcript	c.50-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_178335.3	ENSP00000376249	P3	Q8IVM0-2
CCDC50	ENST00000392456.4 linkuse as main transcript	c.50-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000376250	A1	Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98902

AN:

151914

Hom.:

34096

Cov.:

show subpopulations

Gnomad AFR

AF:

0.863

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.681

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.919

Gnomad SAS

AF:

0.694

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.605

GnomAD3 exomes

AF:

0.628

AC:

157546

AN:

250812

Hom.:

52148

AF XY:

0.616

AC XY:

83504

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.869

Gnomad AMR exome

AF:

0.755

Gnomad ASJ exome

AF:

0.551

Gnomad EAS exome

AF:

0.932

Gnomad SAS exome

AF:

0.681

Gnomad FIN exome

AF:

0.559

Gnomad NFE exome

AF:

0.514

Gnomad OTH exome

AF:

0.579

GnomAD4 exome

AF:

0.545

AC:

786813

AN:

1444388

Hom.:

222768

Cov.:

AF XY:

0.547

AC XY:

393710

AN XY:

719742

show subpopulations

Gnomad4 AFR exome

AF:

0.871

Gnomad4 AMR exome

AF:

0.748

Gnomad4 ASJ exome

AF:

0.549

Gnomad4 EAS exome

AF:

0.898

Gnomad4 SAS exome

AF:

0.680

Gnomad4 FIN exome

AF:

0.553

Gnomad4 NFE exome

AF:

0.502

Gnomad4 OTH exome

AF:

0.568

GnomAD4 genome

AF:

0.651

AC:

99011

AN:

152032

Hom.:

34148

Cov.:

AF XY:

0.659

AC XY:

48939

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.863

Gnomad4 AMR

AF:

0.682

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.919

Gnomad4 SAS

AF:

0.694

Gnomad4 FIN

AF:

0.566

Gnomad4 NFE

AF:

0.516

Gnomad4 OTH

AF:

0.604

Alfa

AF:

0.551

Hom.:

7798

Bravo

AF:

0.670

Asia WGS

AF:

0.803

AC:

2786

AN:

3476

EpiCase

AF:

0.512

EpiControl

AF:

0.509

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	50-4C>G in Intron 01 of CCDC50: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce and has been identified in 49.3% (3462/7020) of European American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs188384). -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant nonsyndromic hearing loss 44

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.1

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000086

dbscSNV1_RF

Benign

0.032

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