NM_198152.5:c.-664-272C>T

Variant names:

• chr3-191328981-G-A
• rs4687210
• NM_198152.5:c.-664-272C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198152.5(UTS2B):​c.-664-272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,162 control chromosomes in the GnomAD database, including 2,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2888 hom., cov: 32)
  • Exomes 𝑓: 0.22 (2 hom.)
• Consequence: UTS2B NM_198152.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.47

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-191328981-G-A is Benign according to our data. Variant chr3-191328981-G-A is described in ClinVar as [Benign]. Clinvar id is 1276371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTS2B	NM_198152.5	c.-664-272C>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
UTS2B	ENST00000340524.10	c.-664-272C>T		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26425 AN: 151984 Hom.: 2887 Cov.: 32

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.217 AC: 13 AN: 60 Hom.: 2 Cov.: 0 AF XY: 0.143 AC XY: 6 AN XY: 42

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.174 AC: 26438 AN: 152102 Hom.: 2888 Cov.: 32 AF XY: 0.173 AC XY: 12893 AN XY: 74354

Gnomad4 AFR AF: 0.0586

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.186

Alfa AF: 0.210 Hom.: 772

Bravo AF: 0.168

Asia WGS AF: 0.0620 AC: 214 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 07, 2019

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	-0.82
CADD	Benign	0.20
DANN	Benign	0.66

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: rs4687210; hg19: chr3-191046770;