chr3-191329946-G-A

Variant names:

• chr3-191329946-G-A
• rs796791217
• NM_178335.3:c.49+223G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_178335.3(CCDC50):​c.49+223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 100,122 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0031 (3 hom., cov: 22)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAd4 at 314 AD,Unknown gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC50	NM_178335.3	MANE Select	c.49+223G>A		intron	N/A	NP_848018.1	Q8IVM0-2
	UTS2B	NM_198152.5	MANE Select	c.-665+468C>T		intron	N/A	NP_937795.2	Q765I0
	CCDC50	NM_174908.4		c.49+223G>A		intron	N/A	NP_777568.1	Q8IVM0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC50	ENST00000392455.9	TSL:1 MANE Select	c.49+223G>A		intron	N/A	ENSP00000376249.4	Q8IVM0-2
	UTS2B	ENST00000340524.10	TSL:2 MANE Select	c.-665+468C>T		intron	N/A	ENSP00000340526.5	Q765I0
	CCDC50	ENST00000392456.4	TSL:1	c.49+223G>A		intron	N/A	ENSP00000376250.4	Q8IVM0-1

Frequencies

GnomAD3 genomes AF: 0.00310 AC: 310 AN: 100046 Hom.: 3 Cov.: 22

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00123

Gnomad ASJ AF: 0.000357

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000726

Gnomad FIN AF: 0.000113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000272

Gnomad OTH AF: 0.00496

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00314 AC: 314 AN: 100122 Hom.: 3 Cov.: 22 AF XY: 0.00286 AC XY: 139 AN XY: 48626

African (AFR) AF: 0.0166 AC: 276 AN: 16660

American (AMR) AF: 0.00123 AC: 12 AN: 9766

Ashkenazi Jewish (ASJ) AF: 0.000357 AC: 1 AN: 2804

East Asian (EAS) AF: 0.00 AC: 0 AN: 1630

South Asian (SAS) AF: 0.000726 AC: 2 AN: 2754

European-Finnish (FIN) AF: 0.000113 AC: 1 AN: 8834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 174

European-Non Finnish (NFE) AF: 0.000272 AC: 15 AN: 55234

Other (OTH) AF: 0.00490 AC: 7 AN: 1428

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.86
PhyloP100		0.33

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: rs796791217; hg19: chr3-191047735;