3-191329261-G-A

Variant names:

• chr3-191329261-G-A
• rs182001630
• ENST00000392456.4:c.-414G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_198152.5(UTS2B):​c.-664-552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 182,350 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (0 hom.)
• Consequence: UTS2B NM_198152.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.47
• Publications: 1 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 3-191329261-G-A is Benign according to our data. Variant chr3-191329261-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1208762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTS2B	NM_198152.5	c.-664-552C>T		intron_variant	Intron 1 of 8	ENST00000340524.10	NP_937795.2
CCDC50	NM_178335.3	c.-414G>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.-664-552C>T		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5
CCDC50	ENST00000392455.9	c.-414G>A		upstream_gene_variant		1	NM_178335.3	ENSP00000376249.4

Frequencies

GnomAD3 genomes AF: 0.00464 AC: 707 AN: 152242 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00676

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.00530 AC: 159 AN: 29990 Hom.: 0 Cov.: 0 AF XY: 0.00435 AC XY: 65 AN XY: 14954

African (AFR) AF: 0.00152 AC: 1 AN: 658

American (AMR) AF: 0.00538 AC: 2 AN: 372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 926

East Asian (EAS) AF: 0.00 AC: 0 AN: 762

South Asian (SAS) AF: 0.000905 AC: 2 AN: 2210

European-Finnish (FIN) AF: 0.00822 AC: 13 AN: 1582

Middle Eastern (MID) AF: 0.0123 AC: 2 AN: 162

European-Non Finnish (NFE) AF: 0.00601 AC: 129 AN: 21454

Other (OTH) AF: 0.00536 AC: 10 AN: 1864

GnomAD4 genome AF: 0.00464 AC: 707 AN: 152360 Hom.: 3 Cov.: 33 AF XY: 0.00467 AC XY: 348 AN XY: 74504

African (AFR) AF: 0.000841 AC: 35 AN: 41600

American (AMR) AF: 0.00248 AC: 38 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.0150 AC: 159 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00676 AC: 460 AN: 68030

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

Alfa AF: 0.00498 Hom.: 0

Bravo AF: 0.00360

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 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	-0.59
CADD	Benign	17
DANN	Benign	0.89
PhyloP100		2.5
PromoterAI		-0.038	Neutral
Mutation Taster		=299/1	polymorphism

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: rs182001630; hg19: chr3-191047050;