3-191329743-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0330

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]

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]

ACMG classification

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	c.49+20A>G		intron_variant		ENST00000392455.9
UTS2B	NM_198152.5	c.-665+671T>C		intron_variant		ENST00000340524.10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100635 AN: 151936 Hom.: 35053 Cov.: 32

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

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.: 38 AF XY: 0.566 AC XY: 408022 AN XY: 720628

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.: 32 AF XY: 0.668 AC XY: 49674 AN XY: 74344

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
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

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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

Other links and lift over

dbSNP: rs9847278; hg19: chr3-191047532;