Genetic Variant NM_001378030.1:c.180+19C>G (chr16-725947-G-C) – ACMG Classification: Benign (-20 pts)

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+19C>G 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 1,564,226 control chromosomes in the GnomAD database, including 46,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3372 hom., cov: 33)

Exomes 𝑓: 0.24 ( 42754 hom. )

Consequence

CCDC78
NM_001378030.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.902

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-725947-G-C is Benign according to our data. Variant chr16-725947-G-C is described in ClinVar as [Benign]. Clinvar id is 257165.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 rank	MANE	Protein	UniProt
CCDC78	NM_001378030.1 link	c.180+19C>G		intron_variant	Intron 2 of 13	ENST00000345165.10	NP_001364959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC78	ENST00000345165.10 link	c.180+19C>G		intron_variant	Intron 2 of 13	5	NM_001378030.1	ENSP00000316851.5		H3BLT8

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30069

AN:

151904

Hom.:

3366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.271

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:

0.249

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.212

AC:

36866

AN:

173960

Hom.:

4535

AF XY:

0.224

AC XY:

20847

AN XY:

93200

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.175

Gnomad EAS exome

AF:

0.00834

Gnomad SAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.254

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.239

AC:

337391

AN:

1412204

Hom.:

42754

Cov.:

AF XY:

0.242

AC XY:

169058

AN XY:

698392

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.0221

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:

30100

AN:

152022

Hom.:

3372

Cov.:

AF XY:

0.199

AC XY:

14796

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.126

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:

0.249

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.152

Hom.:

466

Bravo

AF:

0.181

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital myopathy with internal nuclei and atypical cores

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.89

CADD

Benign

4.3

DANN

Benign

0.26

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