chr3-191375645-A-G

Position:

• chr3-191375645-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000392455.9(CCDC50):​c.976+56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,553,668 control chromosomes in the GnomAD database, including 244,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (32370 hom., cov: 31)
  • Exomes 𝑓: 0.54 (211797 hom.)
• Consequence: CCDC50 ENST00000392455.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.381

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-191375645-A-G is Benign according to our data. Variant chr3-191375645-A-G is described in ClinVar as [Benign]. Clinvar id is 1192702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.976+56A>G		intron_variant		ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4	c.449-4514A>G		intron_variant			NP_777568.1
CCDC50	XM_011512460.2	c.976+56A>G		intron_variant			XP_011510762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9	c.976+56A>G		intron_variant		1	NM_178335.3	ENSP00000376249	P3
CCDC50	ENST00000392456.4	c.449-4514A>G		intron_variant		1		ENSP00000376250	A1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96652 AN: 151778 Hom.: 32305 Cov.: 31

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.541 AC: 758164 AN: 1401770 Hom.: 211797 AF XY: 0.543 AC XY: 378268 AN XY: 696028

Gnomad4 AFR exome AF: 0.822

Gnomad4 AMR exome AF: 0.739

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.891

Gnomad4 SAS exome AF: 0.678

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.565

GnomAD4 genome AF: 0.637 AC: 96776 AN: 151898 Hom.: 32370 Cov.: 31 AF XY: 0.645 AC XY: 47850 AN XY: 74204

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.598

Alfa AF: 0.594 Hom.: 3901

Bravo AF: 0.655

Asia WGS AF: 0.805 AC: 2794 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
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	-0.86
CADD	Benign	0.67
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs293806; hg19: chr3-191093434;