Variant 3-191380750-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_178335.3(CCDC50):c.1137+19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 1,611,598 control chromosomes in the GnomAD database, including 5,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 482 hom., cov: 32)

Exomes 𝑓: 0.063 ( 4642 hom. )

Consequence

CCDC50
NM_178335.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.259

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-191380750-C-G is Benign according to our data. Variant chr3-191380750-C-G is described in ClinVar as [Benign]. Clinvar id is 262930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC50	NM_178335.3 linkuse as main transcript	c.1137+19C>G		intron_variant		ENST00000392455.9	NP_848018.1	Q8IVM0-2
CCDC50	NM_174908.4 linkuse as main transcript	c.609+19C>G		intron_variant			NP_777568.1	Q8IVM0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 linkuse as main transcript	c.1137+19C>G		intron_variant		1	NM_178335.3	ENSP00000376249.4		Q8IVM0-2
CCDC50	ENST00000392456.4 linkuse as main transcript	c.609+19C>G		intron_variant		1		ENSP00000376250.4		Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.0593

AC:

9020

AN:

151994

Hom.:

481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00980

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0483

Gnomad OTH

AF:

0.0523

GnomAD3 exomes

AF:

0.0910

AC:

22680

AN:

249274

Hom.:

1620

AF XY:

0.0927

AC XY:

12493

AN XY:

134748

show subpopulations

Gnomad AFR exome

AF:

0.00964

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.0452

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.0481

Gnomad OTH exome

AF:

0.0693

GnomAD4 exome

AF:

0.0633

AC:

92385

AN:

1459486

Hom.:

4642

Cov.:

AF XY:

0.0664

AC XY:

48192

AN XY:

726058

show subpopulations

Gnomad4 AFR exome

AF:

0.00940

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.0446

Gnomad4 EAS exome

AF:

0.247

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.0463

Gnomad4 OTH exome

AF:

0.0662

GnomAD4 genome

AF:

0.0594

AC:

9033

AN:

152112

Hom.:

482

Cov.:

AF XY:

0.0672

AC XY:

4999

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00980

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.0392

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.171

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.0483

Gnomad4 OTH

AF:

0.0536

Alfa

AF:

0.0538

Hom.:

Bravo

AF:

0.0551

Asia WGS

AF:

0.178

AC:

618

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	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 specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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