rs186382346

Variant names:

• chr3-191329292-G-A
• rs186382346
• ENST00000392456.4:c.-383G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_198152.5(UTS2B):​c.-664-583C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 203,228 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (0 hom.)
• Consequence: UTS2B NM_198152.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 3-191329292-G-A is Benign according to our data. Variant chr3-191329292-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196503.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTS2B	NM_198152.5	c.-664-583C>T		intron_variant	Intron 1 of 8	ENST00000340524.10	NP_937795.2
CCDC50	NM_178335.3	c.-383G>A		upstream_gene_variant		ENST00000392455.9	NP_848018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTS2B	ENST00000340524.10	c.-664-583C>T		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5
CCDC50	ENST00000392455.9	c.-383G>A		upstream_gene_variant		1	NM_178335.3	ENSP00000376249.4

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 540 AN: 152236 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00536

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00548

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.00421 AC: 214 AN: 50874 Hom.: 0 Cov.: 0 AF XY: 0.00429 AC XY: 110 AN XY: 25642

African (AFR) AF: 0.000700 AC: 1 AN: 1428

American (AMR) AF: 0.00647 AC: 6 AN: 928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1802

East Asian (EAS) AF: 0.00 AC: 0 AN: 2400

South Asian (SAS) AF: 0.00 AC: 0 AN: 2320

European-Finnish (FIN) AF: 0.00415 AC: 13 AN: 3134

Middle Eastern (MID) AF: 0.00329 AC: 1 AN: 304

European-Non Finnish (NFE) AF: 0.00524 AC: 184 AN: 35092

Other (OTH) AF: 0.00260 AC: 9 AN: 3466

GnomAD4 genome AF: 0.00354 AC: 540 AN: 152354 Hom.: 2 Cov.: 33 AF XY: 0.00361 AC XY: 269 AN XY: 74496

African (AFR) AF: 0.000793 AC: 33 AN: 41600

American (AMR) AF: 0.00425 AC: 65 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00536 AC: 57 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00548 AC: 373 AN: 68018

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00805 Hom.: 2

Bravo AF: 0.00327

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 02, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		1.6
PromoterAI		0.031	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs186382346; hg19: chr3-191047081;