chr3-191328956-C-T

Variant names:

• chr3-191328956-C-T
• rs62617841
• NM_198152.5:c.-664-247G>A

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.-664-247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0602 in 152,262 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (429 hom., cov: 32)
  • Exomes 𝑓: 0.11 (2 hom.)
• Consequence: UTS2B NM_198152.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.769

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=-0.77).
• BP6: Variant 3-191328956-C-T is Benign according to our data. Variant chr3-191328956-C-T is described in ClinVar as [Benign]. Clinvar id is 1268024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTS2B	NM_198152.5	c.-664-247G>A		intron_variant	Intron 1 of 8	ENST00000340524.10	NP_937795.2
UTS2B	XM_017006091.2	c.-413G>A		5_prime_UTR_variant	Exon 1 of 8		XP_016861580.1
UTS2B	XM_011512631.3	c.-413G>A		5_prime_UTR_variant	Exon 1 of 8		XP_011510933.1
UTS2B	XM_047447899.1	c.-260-247G>A		intron_variant	Intron 1 of 7		XP_047303855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTS2B	ENST00000340524.10	c.-664-247G>A		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5

Frequencies

GnomAD3 genomes AF: 0.0602 AC: 9157 AN: 152090 Hom.: 429 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0658

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0489

GnomAD4 exome AF: 0.111 AC: 6 AN: 54 Hom.: 2 Cov.: 0 AF XY: 0.0833 AC XY: 3 AN XY: 36

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0602 AC: 9165 AN: 152208 Hom.: 429 Cov.: 32 AF XY: 0.0674 AC XY: 5019 AN XY: 74414

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.0658

Gnomad4 ASJ AF: 0.0882

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0576

Gnomad4 OTH AF: 0.0503

Alfa AF: 0.0605 Hom.: 42

Bravo AF: 0.0524

Asia WGS AF: 0.157 AC: 544 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 10, 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	-0.77
CADD	Benign	7.2
DANN	Benign	0.67

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: rs62617841; hg19: chr3-191046745;