Genetic Variant UTS2B:c.-664-295C>G (chr3-191329004-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198152.5(UTS2B):c.-664-295C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,236 control chromosomes in the GnomAD database, including 18,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 18678 hom., cov: 33)

Exomes 𝑓: 0.34 ( 8 hom. )

Consequence

UTS2B
NM_198152.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.952

Variant links:

Genes affected

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]

UTS2B links:

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]

CCDC50 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-191329004-G-C is Benign according to our data. Variant chr3-191329004-G-C is described in ClinVar as [Benign]. Clinvar id is 1273417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTS2B	NM_198152.5 link	c.-664-295C>G		intron_variant	Intron 1 of 8	ENST00000340524.10	NP_937795.2	Q765I0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTS2B	ENST00000340524.10 link	c.-664-295C>G		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5		Q765I0

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68233

AN:

152024

Hom.:

18653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.712

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.467

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.917

Gnomad SAS

AF:

0.575

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.400

GnomAD4 exome

AF:

0.340

AC:

AN:

Hom.:

Cov.:

AF XY:

0.348

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.667

Gnomad4 SAS exome

AF:

0.750

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.833

GnomAD4 genome

AF:

0.449

AC:

68305

AN:

152142

Hom.:

18678

Cov.:

AF XY:

0.456

AC XY:

33909

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.712

Gnomad4 AMR

AF:

0.467

Gnomad4 ASJ

AF:

0.309

Gnomad4 EAS

AF:

0.917

Gnomad4 SAS

AF:

0.575

Gnomad4 FIN

AF:

0.287

Gnomad4 NFE

AF:

0.277

Gnomad4 OTH

AF:

0.403

Alfa

AF:

0.351

Hom.:

1403

Bravo

AF:

0.473

Asia WGS

AF:

0.729

AC:

2530

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: 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

-0.83

CADD

Benign

1.7

DANN

Benign

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over