chr3-191329743-A-G

Variant names:

• chr3-191329743-A-G
• rs9847278
• NM_178335.3:c.49+20A>G

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -0.0330
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 262931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178335.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC50	NM_178335.3	MANE Select	c.49+20A>G		intron	N/A	NP_848018.1
	UTS2B	NM_198152.5	MANE Select	c.-665+671T>C		intron	N/A	NP_937795.2
	CCDC50	NM_174908.4		c.49+20A>G		intron	N/A	NP_777568.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC50	ENST00000392455.9	TSL:1 MANE Select	c.49+20A>G		intron	N/A	ENSP00000376249.4
	UTS2B	ENST00000340524.10	TSL:2 MANE Select	c.-665+671T>C		intron	N/A	ENSP00000340526.5
	CCDC50	ENST00000392456.4	TSL:1	c.49+20A>G		intron	N/A	ENSP00000376250.4

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

GnomAD2 exomes AF: 0.641 AC: 144582 AN: 225496 AF XY: 0.628

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 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

African (AFR) AF: 0.867 AC: 28814 AN: 33222

American (AMR) AF: 0.769 AC: 33277 AN: 43264

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 14133 AN: 25842

East Asian (EAS) AF: 0.897 AC: 35179 AN: 39232

South Asian (SAS) AF: 0.677 AC: 56974 AN: 84190

European-Finnish (FIN) AF: 0.567 AC: 29570 AN: 52134

Middle Eastern (MID) AF: 0.527 AC: 3021 AN: 5736

European-Non Finnish (NFE) AF: 0.527 AC: 582979 AN: 1107176

Other (OTH) AF: 0.592 AC: 35439 AN: 59906

GnomAD4 genome AF: 0.662 AC: 100734 AN: 152054 Hom.: 35098 Cov.: 32 AF XY: 0.668 AC XY: 49674 AN XY: 74344

African (AFR) AF: 0.859 AC: 35671 AN: 41536

American (AMR) AF: 0.706 AC: 10786 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1903 AN: 3470

East Asian (EAS) AF: 0.920 AC: 4743 AN: 5156

South Asian (SAS) AF: 0.693 AC: 3339 AN: 4818

European-Finnish (FIN) AF: 0.573 AC: 6051 AN: 10568

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36442 AN: 67902

Other (OTH) AF: 0.621 AC: 1312 AN: 2114

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

Submissions by phenotype

not provided Benign:3

Jun 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.66
PhyloP100		-0.033
PromoterAI		0.048	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: rs9847278; hg19: chr3-191047532;