rs11542549

Positions:

• chr3-191358113-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_178335.3(CCDC50):​c.228C>T​(p.Arg76=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,613,326 control chromosomes in the GnomAD database, including 77,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (6804 hom., cov: 31)
  • Exomes 𝑓: 0.31 (70808 hom.)
• Consequence: CCDC50 NM_178335.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0720

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 3-191358113-C-T is Benign according to our data. Variant chr3-191358113-C-T is described in ClinVar as [Benign]. Clinvar id is 48153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.072 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.228C>T	p.Arg76=	synonymous_variant	3/12	ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4	c.228C>T	p.Arg76=	synonymous_variant	3/11		NP_777568.1
CCDC50	XM_011512460.2	c.228C>T	p.Arg76=	synonymous_variant	3/8		XP_011510762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9	c.228C>T	p.Arg76=	synonymous_variant	3/12	1	NM_178335.3	ENSP00000376249	P3
CCDC50	ENST00000392456.4	c.228C>T	p.Arg76=	synonymous_variant	3/11	1		ENSP00000376250	A1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45350 AN: 151782 Hom.: 6791 Cov.: 31

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.302 AC: 75895 AN: 250986 Hom.: 11716 AF XY: 0.299 AC XY: 40602 AN XY: 135638

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.250

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.326

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.311

GnomAD4 exome AF: 0.309 AC: 451791 AN: 1461426 Hom.: 70808 Cov.: 36 AF XY: 0.307 AC XY: 223342 AN XY: 727028

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.365

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.299 AC: 45414 AN: 151900 Hom.: 6804 Cov.: 31 AF XY: 0.300 AC XY: 22270 AN XY: 74228

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.314

Alfa AF: 0.317 Hom.: 4730

Bravo AF: 0.300

Asia WGS AF: 0.279 AC: 968 AN: 3478

EpiCase AF: 0.318

EpiControl AF: 0.312

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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	Arg76Arg in Exon 03 of CCDC50: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 32.0% (2245/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs11542549). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs11542549; hg19: chr3-191075902; COSMIC: COSV66667449; COSMIC: COSV66667449;