chr3-191328956-C-T

Variant names:

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

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.-664-247G>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
• Publications: 0 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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal dominant nonsyndromic hearing loss 44

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.77).
• BP6: Variant 3-191328956-C-T is Benign according to our data. Variant chr3-191328956-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

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.-664-247G>A		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.-664-247G>A		intron	N/A	ENSP00000340526.5	Q765I0
	UTS2B	ENST00000899455.1		c.-260-247G>A		intron	N/A	ENSP00000569514.1
	UTS2B	ENST00000432514.5	TSL:5	c.-831-247G>A		intron	N/A	ENSP00000401028.1	C9JU87

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

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: 1.00 AC: 2 AN: 2

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.111 AC: 4 AN: 36

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0109 AC: 454 AN: 41548

American (AMR) AF: 0.0658 AC: 1007 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 306 AN: 3470

East Asian (EAS) AF: 0.192 AC: 994 AN: 5166

South Asian (SAS) AF: 0.187 AC: 898 AN: 4808

European-Finnish (FIN) AF: 0.137 AC: 1452 AN: 10600

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0576 AC: 3917 AN: 68008

Other (OTH) AF: 0.0503 AC: 106 AN: 2108

Alfa AF: 0.0605 Hom.: 42

Bravo AF: 0.0524

Asia WGS AF: 0.157 AC: 544 AN: 3478

ClinVar

ClinVar submissions

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	-0.77
CADD	Benign	7.2
DANN	Benign	0.67
PhyloP100		0.77
PromoterAI		-0.012	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: rs62617841; hg19: chr3-191046745;