3-191329292-G-A

Variant names:

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -10 ACMG points: 0P and 10B. BS2BP4_StrongBP6_Moderate

The ENST00000392456.4(CCDC50):c.-383G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.00371 (AC=754) in the gnomAD database across 203,228 control chromosomes, including 2 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.00502. 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 0.0035 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 0 hom. )

Consequence

CCDC50
ENST00000392456.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.62

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 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 -10 ACMG points.

BP4

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

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 = 2.; Very high cumulative gnomAD AC = 754 (any gene).

Variant Effect in Transcripts

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

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UTS2B	NM_198152.5	MANE Select	c.-664-583C>T	intron	N/A	NP_937795.2	Q765I0
CCDC50	NM_178335.3	MANE Select	c.-383G>A	upstream_gene	N/A	NP_848018.1	Q8IVM0-2
CCDC50	NM_174908.4		c.-383G>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.-383G>A	5_prime_UTR	Exon 1 of 11	ENSP00000376250.4	Q8IVM0-1
UTS2B	ENST00000340524.10	TSL:2 MANE Select	c.-664-583C>T	intron	N/A	ENSP00000340526.5	Q765I0
UTS2B	ENST00000899455.1		c.-260-583C>T	intron	N/A	ENSP00000569514.1

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

540

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00536

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00548

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.00421

AC:

214

AN:

50874

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

110

AN XY:

25642

show subpopulations

African (AFR)

AF:

0.000700

AC:

AN:

1428

American (AMR)

AF:

0.00647

AC:

AN:

928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1802

East Asian (EAS)

AF:

0.00

AC:

AN:

2400

South Asian (SAS)

AF:

0.00

AC:

AN:

2320

European-Finnish (FIN)

AF:

0.00415

AC:

AN:

3134

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.00524

AC:

184

AN:

35092

Other (OTH)

AF:

0.00260

AC:

AN:

3466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.00354

AC:

540

AN:

152354

Hom.:

Cov.:

AF XY:

0.00361

AC XY:

269

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000793

AC:

AN:

41600

American (AMR)

AF:

0.00425

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00536

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00548

AC:

373

AN:

68018

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00805

Hom.:

Bravo

AF:

0.00327

Local populations

Turkish Variome

AF:

0.000647

AC:

AN:

1546

Hom.:

ABraOM SABE-WGS-1171

AF:

0.00214

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

-0.64

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

1.6

PromoterAI

0.031

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over