3-191329954-G-A

Variant names:

• chr3-191329954-G-A
• rs115986233
• NM_178335.3:c.49+231G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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]

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.49+231G>A		intron_variant	Intron 1 of 11	ENST00000392455.9	NP_848018.1
UTS2B	NM_198152.5	c.-665+460C>T		intron_variant	Intron 1 of 8	ENST00000340524.10	NP_937795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9	c.49+231G>A		intron_variant	Intron 1 of 11	1	NM_178335.3	ENSP00000376249.4
UTS2B	ENST00000340524.10	c.-665+460C>T		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5
CCDC50	ENST00000392456.4	c.49+231G>A		intron_variant	Intron 1 of 10	1		ENSP00000376250.4
UTS2B	ENST00000432514.5	c.-832+460C>T		intron_variant	Intron 1 of 6	5		ENSP00000401028.1

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

African (AFR) AF: 0.174 AC: 6467 AN: 37154

American (AMR) AF: 0.204 AC: 2756 AN: 13490

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 437 AN: 3340

East Asian (EAS) AF: 0.484 AC: 2094 AN: 4324

South Asian (SAS) AF: 0.239 AC: 947 AN: 3970

European-Finnish (FIN) AF: 0.0780 AC: 671 AN: 8608

Middle Eastern (MID) AF: 0.179 AC: 48 AN: 268

European-Non Finnish (NFE) AF: 0.145 AC: 9306 AN: 64168

Other (OTH) AF: 0.170 AC: 326 AN: 1914

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

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.89
PhyloP100		-0.21
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: rs115986233; hg19: chr3-191047743;