Variant 16-724520-C-T 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.766-11G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,589,550 control chromosomes in the GnomAD database, including 203,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18866 hom., cov: 33)

Exomes 𝑓: 0.50 ( 184471 hom. )

Consequence

CCDC78
NM_001378030.1 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0005553

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.61

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=-0.91).

BP6

Variant 16-724520-C-T is Benign according to our data. Variant chr16-724520-C-T is described in ClinVar as [Benign]. Clinvar id is 257169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-724520-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 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.766-11G>A		splice_polypyrimidine_tract_variant, 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.766-11G>A		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001378030.1	ENSP00000316851	A2

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73694

AN:

151906

Hom.:

18839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.579

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.762

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.451

GnomAD3 exomes

AF:

0.574

AC:

120458

AN:

209688

Hom.:

36858

AF XY:

0.573

AC XY:

67191

AN XY:

117176

show subpopulations

Gnomad AFR exome

AF:

0.399

Gnomad AMR exome

AF:

0.715

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.816

Gnomad SAS exome

AF:

0.761

Gnomad FIN exome

AF:

0.612

Gnomad NFE exome

AF:

0.465

Gnomad OTH exome

AF:

0.495

GnomAD4 exome

AF:

0.495

AC:

712055

AN:

1437526

Hom.:

184471

Cov.:

AF XY:

0.502

AC XY:

358898

AN XY:

714906

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.695

Gnomad4 ASJ exome

AF:

0.397

Gnomad4 EAS exome

AF:

0.799

Gnomad4 SAS exome

AF:

0.753

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.460

Gnomad4 OTH exome

AF:

0.491

GnomAD4 genome

AF:

0.485

AC:

73760

AN:

152024

Hom.:

18866

Cov.:

AF XY:

0.501

AC XY:

37198

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.393

Gnomad4 AMR

AF:

0.580

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.808

Gnomad4 SAS

AF:

0.763

Gnomad4 FIN

AF:

0.603

Gnomad4 NFE

AF:

0.464

Gnomad4 OTH

AF:

0.456

Alfa

AF:

0.478

Hom.:

3306

Bravo

AF:

0.472

Asia WGS

AF:

0.741

AC:

2572

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital myopathy with internal nuclei and atypical cores

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00056

dbscSNV1_RF

Benign

0.038

SpliceAI score (max)

0.080

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