Variant chr3-191329743-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178335.3(CCDC50):c.49+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 1,602,756 control chromosomes in the GnomAD database, including 272,951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 35098 hom., cov: 32)

Exomes 𝑓: 0.56 ( 237853 hom. )

Consequence

CCDC50
NM_178335.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0330

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-191329743-A-G is Benign according to our data. Variant chr3-191329743-A-G is described in ClinVar as [Benign]. Clinvar id is 262931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-191329743-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC50	NM_178335.3 linkuse as main transcript	c.49+20A>G		intron_variant		ENST00000392455.9
UTS2B	NM_198152.5 linkuse as main transcript	c.-665+671T>C		intron_variant		ENST00000340524.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
UTS2B	ENST00000340524.10 linkuse as main transcript	c.-665+671T>C	intron_variant	2	NM_198152.5	P1
CCDC50	ENST00000392455.9 linkuse as main transcript	c.49+20A>G	intron_variant	1	NM_178335.3	P3	Q8IVM0-2
CCDC50	ENST00000392456.4 linkuse as main transcript	c.49+20A>G	intron_variant	1		A1	Q8IVM0-1
UTS2B	ENST00000432514.5 linkuse as main transcript	c.-832+671T>C	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.662

AC:

100635

AN:

151936

Hom.:

35053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.859

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.705

Gnomad ASJ

AF:

0.548

Gnomad EAS

AF:

0.920

Gnomad SAS

AF:

0.693

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.537

Gnomad OTH

AF:

0.621

GnomAD3 exomes

AF:

0.641

AC:

144582

AN:

225496

Hom.:

48422

AF XY:

0.628

AC XY:

77121

AN XY:

122840

show subpopulations

Gnomad AFR exome

AF:

0.864

Gnomad AMR exome

AF:

0.777

Gnomad ASJ exome

AF:

0.547

Gnomad EAS exome

AF:

0.932

Gnomad SAS exome

AF:

0.679

Gnomad FIN exome

AF:

0.571

Gnomad NFE exome

AF:

0.531

Gnomad OTH exome

AF:

0.598

GnomAD4 exome

AF:

0.565

AC:

819386

AN:

1450702

Hom.:

237853

Cov.:

AF XY:

0.566

AC XY:

408022

AN XY:

720628

show subpopulations

Gnomad4 AFR exome

AF:

0.867

Gnomad4 AMR exome

AF:

0.769

Gnomad4 ASJ exome

AF:

0.547

Gnomad4 EAS exome

AF:

0.897

Gnomad4 SAS exome

AF:

0.677

Gnomad4 FIN exome

AF:

0.567

Gnomad4 NFE exome

AF:

0.527

Gnomad4 OTH exome

AF:

0.592

GnomAD4 genome

AF:

0.662

AC:

100734

AN:

152054

Hom.:

35098

Cov.:

AF XY:

0.668

AC XY:

49674

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.859

Gnomad4 AMR

AF:

0.706

Gnomad4 ASJ

AF:

0.548

Gnomad4 EAS

AF:

0.920

Gnomad4 SAS

AF:

0.693

Gnomad4 FIN

AF:

0.573

Gnomad4 NFE

AF:

0.537

Gnomad4 OTH

AF:

0.621

Alfa

AF:

0.592

Hom.:

5118

Bravo

AF:

0.683

Asia WGS

AF:

0.802

AC:

2782

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

DANN

Benign

0.66

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over