chr3-191381858-A-G

Variant names:

• chr3-191381858-A-G
• rs407226
• NM_178335.3:c.1243-888A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178335.3(CCDC50):​c.1243-888A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,910 control chromosomes in the GnomAD database, including 27,035 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (27035 hom., cov: 31)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 44

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178335.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC50	NM_178335.3	MANE Select	c.1243-888A>G		intron	N/A	NP_848018.1
	CCDC50	NM_174908.4		c.715-888A>G		intron	N/A	NP_777568.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC50	ENST00000392455.9	TSL:1 MANE Select	c.1243-888A>G		intron	N/A	ENSP00000376249.4
	CCDC50	ENST00000392456.4	TSL:1	c.715-888A>G		intron	N/A	ENSP00000376250.4

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87659 AN: 151792 Hom.: 26981 Cov.: 31

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.504

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

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.578 AC: 87768 AN: 151910 Hom.: 27035 Cov.: 31 AF XY: 0.578 AC XY: 42879 AN XY: 74232

African (AFR) AF: 0.806 AC: 33422 AN: 41458

American (AMR) AF: 0.567 AC: 8640 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1750 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3428 AN: 5156

South Asian (SAS) AF: 0.522 AC: 2510 AN: 4812

European-Finnish (FIN) AF: 0.444 AC: 4679 AN: 10530

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31712 AN: 67918

Other (OTH) AF: 0.544 AC: 1147 AN: 2110

Alfa AF: 0.540 Hom.: 3029

Bravo AF: 0.599

Asia WGS AF: 0.626 AC: 2171 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.56
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs407226; hg19: chr3-191099647;