Variant rs12448311 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378030.1(CCDC78):c.180+12G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,560,678 control chromosomes in the GnomAD database, including 46,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3373 hom., cov: 33)

Exomes 𝑓: 0.24 ( 42641 hom. )

Consequence

CCDC78
NM_001378030.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.34

Variant links:

Genes affected

CCDC78 (HGNC:14153): (coiled-coil domain containing 78) Involved in de novo centriole assembly involved in multi-ciliated epithelial cell differentiation and skeletal muscle contraction. Located in several cellular components, including centriole; deuterosome; and sarcolemma. Implicated in centronuclear myopathy 4. [provided by Alliance of Genome Resources, Apr 2022]

CCDC78 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 (BayesDel_noAF=-0.83).

BP6

Variant 16-725954-C-A is Benign according to our data. Variant chr16-725954-C-A is described in ClinVar as [Benign]. Clinvar id is 257164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC78	NM_001378030.1 linkuse as main transcript	c.180+12G>T		intron_variant		ENST00000345165.10	NP_001364959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC78	ENST00000345165.10 linkuse as main transcript	c.180+12G>T		intron_variant		5	NM_001378030.1	ENSP00000316851	A2

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30060

AN:

151908

Hom.:

3367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.0127

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.210

AC:

35590

AN:

169314

Hom.:

4368

AF XY:

0.222

AC XY:

20011

AN XY:

90258

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.00819

Gnomad SAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.239

AC:

336507

AN:

1408652

Hom.:

42641

Cov.:

AF XY:

0.242

AC XY:

168460

AN XY:

696156

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.0222

Gnomad4 SAS exome

AF:

0.320

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.250

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.198

AC:

30091

AN:

152026

Hom.:

3373

Cov.:

AF XY:

0.199

AC XY:

14799

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.183

Gnomad4 EAS

AF:

0.0129

Gnomad4 SAS

AF:

0.317

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.231

Hom.:

808

Bravo

AF:

0.181

Asia WGS

AF:

0.191

AC:

663

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital myopathy with internal nuclei and atypical cores

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.45

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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