rs112961570

Variant names:

• chr3-191329971-A-G
• rs112961570
• NM_178335.3:c.49+248A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_178335.3(CCDC50):​c.49+248A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 134,700 control chromosomes in the GnomAD database, including 228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.031 (228 hom., cov: 28)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.181
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-191329971-A-G is Benign according to our data. Variant chr3-191329971-A-G is described in ClinVar as [Benign]. Clinvar id is 1252176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC50	NM_178335.3	c.49+248A>G		intron_variant	Intron 1 of 11	ENST00000392455.9	NP_848018.1
UTS2B	NM_198152.5	c.-665+443T>C		intron_variant	Intron 1 of 8	ENST00000340524.10	NP_937795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9	c.49+248A>G		intron_variant	Intron 1 of 11	1	NM_178335.3	ENSP00000376249.4
UTS2B	ENST00000340524.10	c.-665+443T>C		intron_variant	Intron 1 of 8	2	NM_198152.5	ENSP00000340526.5
CCDC50	ENST00000392456.4	c.49+248A>G		intron_variant	Intron 1 of 10	1		ENSP00000376250.4
UTS2B	ENST00000432514.5	c.-832+443T>C		intron_variant	Intron 1 of 6	5		ENSP00000401028.1

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4219 AN: 134620 Hom.: 228 Cov.: 28

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.000310

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000296

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0142

Gnomad NFE AF: 0.000589

Gnomad OTH AF: 0.0172

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

GnomAD4 genome AF: 0.0313 AC: 4219 AN: 134700 Hom.: 228 Cov.: 28 AF XY: 0.0306 AC XY: 1985 AN XY: 64912

African (AFR) AF: 0.106 AC: 4011 AN: 37878

American (AMR) AF: 0.0102 AC: 134 AN: 13172

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 1 AN: 3226

East Asian (EAS) AF: 0.00 AC: 0 AN: 2638

South Asian (SAS) AF: 0.000298 AC: 1 AN: 3360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8582

Middle Eastern (MID) AF: 0.0152 AC: 4 AN: 264

European-Non Finnish (NFE) AF: 0.000573 AC: 36 AN: 62840

Other (OTH) AF: 0.0171 AC: 32 AN: 1870

Alfa AF: 0.0213 Hom.: 12

Bravo AF: 0.0323

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 25, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.6
DANN	Benign	0.64
PhyloP100		-0.18
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: rs112961570; hg19: chr3-191047760;