3-191329954-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_178335.3(CCDC50):c.49+231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 138,092 control chromosomes in the GnomAD database, including 2,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2594 hom., cov: 22)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.211

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]

UTS2B (HGNC:30894): (urotensin 2B) Predicted to enable G protein-coupled receptor binding activity. Predicted to be involved in regulation of blood pressure. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-191329954-G-A is Benign according to our data. Variant chr3-191329954-G-A is described in ClinVar as [Benign]. Clinvar id is 1286281.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC50	NM_178335.3	c.49+231G>A		intron_variant		ENST00000392455.9
UTS2B	NM_198152.5	c.-665+460C>T		intron_variant		ENST00000340524.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTS2B	ENST00000340524.10	c.-665+460C>T		intron_variant		2	NM_198152.5	P1
CCDC50	ENST00000392455.9	c.49+231G>A		intron_variant		1	NM_178335.3	P3
CCDC50	ENST00000392456.4	c.49+231G>A		intron_variant		1		A1
UTS2B	ENST00000432514.5	c.-832+460C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.168 AC: 23121 AN: 137988 Hom.: 2588 Cov.: 22

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.168 AC: 23143 AN: 138092 Hom.: 2594 Cov.: 22 AF XY: 0.168 AC XY: 11155 AN XY: 66532

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.0780

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.170

Alfa AF: 0.0581 Hom.: 61

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.7
Dann	Benign	0.89

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: rs115986233; hg19: chr3-191047743;