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. The variant received -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
• Publications: 17 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, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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=-0.82).
• BP6: Variant 3-191328981-G-A is Benign according to our data. Variant chr3-191328981-G-A is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198152.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTS2B	NM_198152.5	MANE Select	c.-664-272C>T		intron	N/A	NP_937795.2	Q765I0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTS2B	ENST00000340524.10	TSL:2 MANE Select	c.-664-272C>T		intron	N/A	ENSP00000340526.5	Q765I0
	UTS2B	ENST00000899455.1		c.-260-272C>T		intron	N/A	ENSP00000569514.1
	UTS2B	ENST00000432514.5	TSL:5	c.-831-272C>T		intron	N/A	ENSP00000401028.1	C9JU87

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.400 AC: 4 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.237 AC: 9 AN: 38

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.0586 AC: 2430 AN: 41498

American (AMR) AF: 0.215 AC: 3293 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 841 AN: 3466

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5172

South Asian (SAS) AF: 0.115 AC: 555 AN: 4820

European-Finnish (FIN) AF: 0.250 AC: 2641 AN: 10580

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16072 AN: 67966

Other (OTH) AF: 0.186 AC: 393 AN: 2110

Alfa AF: 0.210 Hom.: 772

Bravo AF: 0.168

Asia WGS AF: 0.0620 AC: 214 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.20
DANN	Benign	0.66
PhyloP100		-2.5
PromoterAI		-0.34	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: rs4687210; hg19: chr3-191046770;