rs114502673

Positions:

chr3-191380871-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000392455.9(CCDC50):c.1181A>G(p.Lys394Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00623 in 1,613,084 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 89 hom. )

Consequence

CCDC50
ENST00000392455.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006295413).

BP6

Variant 3-191380871-A-G is Benign according to our data. Variant chr3-191380871-A-G is described in ClinVar as [Benign]. Clinvar id is 162860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-191380871-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00385 (586/152226) while in subpopulation SAS AF= 0.023 (111/4830). AF 95% confidence interval is 0.0195. There are 4 homozygotes in gnomad4. There are 276 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 586 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC50	NM_178335.3 linkuse as main transcript	c.1181A>G	p.Lys394Arg	missense_variant	9/12	ENST00000392455.9	NP_848018.1
CCDC50	NM_174908.4 linkuse as main transcript	c.653A>G	p.Lys218Arg	missense_variant	8/11		NP_777568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC50	ENST00000392455.9 linkuse as main transcript	c.1181A>G	p.Lys394Arg	missense_variant	9/12	1	NM_178335.3	ENSP00000376249	P3	Q8IVM0-2
CCDC50	ENST00000392456.4 linkuse as main transcript	c.653A>G	p.Lys218Arg	missense_variant	8/11	1		ENSP00000376250	A1	Q8IVM0-1

Frequencies

GnomAD3 genomes

AF:

0.00383

AC:

583

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0225

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00556

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00605

AC:

1515

AN:

250402

Hom.:

AF XY:

0.00724

AC XY:

980

AN XY:

135362

show subpopulations

Gnomad AFR exome

AF:

0.000929

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0242

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00549

Gnomad OTH exome

AF:

0.00624

GnomAD4 exome

AF:

0.00648

AC:

9468

AN:

1460858

Hom.:

Cov.:

AF XY:

0.00727

AC XY:

5284

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.000748

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00575

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0258

Gnomad4 FIN exome

AF:

0.000449

Gnomad4 NFE exome

AF:

0.00586

Gnomad4 OTH exome

AF:

0.00654

GnomAD4 genome

AF:

0.00385

AC:

586

AN:

152226

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00556

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00556

Hom.:

Bravo

AF:

0.00344

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.00639

AC:

776

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00627

EpiControl

AF:

0.00599

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 11, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 07, 2013	Lys394Arg in Exon 09 of CCDC50: This variant is not expected to have clinical si gnificance because it has been identified in 0.4% (30/7018) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs114502673). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0047

.;T

Eigen

Benign

0.090

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0063

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;M

MutationTaster

Benign

0.65

N;N

PrimateAI

Uncertain

0.61

REVEL

Benign

0.092

Polyphen

0.70

P;B

MVP

0.39

MPC

0.46

ClinPred

0.019

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.019

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