chr3-191329004-G-C

Variant names:

• chr3-191329004-G-C
• rs6779820
• NM_198152.5:c.-664-295C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.952
• Publications: 3 publications found

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]

CCDC50 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 44

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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	c.-664-295C>G		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.-664-295C>G		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68233 AN: 152024 Hom.: 18653 Cov.: 33

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: 32 AN: 94 Hom.: 8 Cov.: 0 AF XY: 0.348 AC XY: 23 AN XY: 66

African (AFR) AF: 0.667 AC: 4 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.750 AC: 3 AN: 4

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.286 AC: 20 AN: 70

Other (OTH) AF: 0.833 AC: 5 AN: 6

GnomAD4 genome AF: 0.449 AC: 68305 AN: 152142 Hom.: 18678 Cov.: 33 AF XY: 0.456 AC XY: 33909 AN XY: 74386

African (AFR) AF: 0.712 AC: 29557 AN: 41506

American (AMR) AF: 0.467 AC: 7143 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3466

East Asian (EAS) AF: 0.917 AC: 4746 AN: 5176

South Asian (SAS) AF: 0.575 AC: 2764 AN: 4810

European-Finnish (FIN) AF: 0.287 AC: 3044 AN: 10588

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18846 AN: 67990

Other (OTH) AF: 0.403 AC: 851 AN: 2114

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

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
PhyloP100		-0.95
PromoterAI		-0.0032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs6779820; hg19: chr3-191046793;