rs368705093

Variant names:

Variant summary

Our verdict is The variant received -8 classification points (ACMG Germline Pathogenicity v2019). BS2BP4_ModerateBP6_Moderate

The ENST00000392456.4(CCDC50):c.-457G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Note: ENST00000392456.4 is not a MANE Select or MANE Plus Clinical transcript for CCDC50; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.00366 (AC=583) in the gnomAD database across 159,276 control chromosomes, including 3 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.0116. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

CCDC50
ENST00000392456.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.17

Publications

0 publications found

Variant links:

Genes affected

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
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss 44
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

CCDC50 links:

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]

UTS2B links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000392456.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -8 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).

BP6

ClinVar 1-star benign — moderate (BP6); ClinVar germline classification: Benign/Likely Benign, 1 star(s).

BS2

≥2 homozygotes in gnomAD — observed in healthy adults (BS2); GnomAD homozygous count = 3.; Very high cumulative gnomAD AC = 583 (any gene).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000392456.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UTS2B	NM_198152.5	MANE Select	c.-664-509C>T	intron	N/A	NP_937795.2	Q765I0
CCDC50	NM_178335.3	MANE Select	c.-457G>A	upstream_gene	N/A	NP_848018.1	Q8IVM0-2
CCDC50	NM_174908.4		c.-457G>A	upstream_gene	N/A	NP_777568.1	Q8IVM0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC50	ENST00000392456.4	TSL:1	c.-457G>A	5_prime_UTR	Exon 1 of 11	ENSP00000376250.4	Q8IVM0-1
UTS2B	ENST00000340524.10	TSL:2 MANE Select	c.-664-509C>T	intron	N/A	ENSP00000340526.5	Q765I0
UTS2B	ENST00000899455.1		c.-260-509C>T	intron	N/A	ENSP00000569514.1	Q765I0

Frequencies

GnomAD3 genomes

AF:

0.00383

AC:

583

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.000288

AC:

AN:

6948

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

AN XY:

3492

show subpopulations

African (AFR)

AF:

0.00649

AC:

AN:

154

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

184

East Asian (EAS)

AF:

0.00

AC:

AN:

124

South Asian (SAS)

AF:

0.00

AC:

AN:

368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

5310

Other (OTH)

AF:

0.00219

AC:

AN:

456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00381

AC:

581

AN:

152328

Hom.:

Cov.:

AF XY:

0.00366

AC XY:

273

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0125

AC:

518

AN:

41578

American (AMR)

AF:

0.00229

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68016

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

110

138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00428

Asia WGS

AF:

0.00202

AC:

AN:

3478

Local populations

Turkish Variome

AF:

0.000647

AC:

AN:

1546

Hom.:

ABraOM SABE-WGS-1171

AF:

0.00769

AC:

AN:

2342

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

3.2

PromoterAI

-0.026

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over