Genetic Variant CCDC78:c.1302-59G>A (chr16-722848-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378030.1(CCDC78):c.1302-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00494 in 1,607,472 control chromosomes in the GnomAD database, including 327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 174 hom., cov: 34)

Exomes 𝑓: 0.0027 ( 153 hom. )

Consequence

CCDC78
NM_001378030.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.60

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

congenital myopathy with internal nuclei and atypical cores
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
centronuclear myopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CCDC78 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-722848-C-T is Benign according to our data. Variant chr16-722848-C-T is described in ClinVar as Benign. ClinVar VariationId is 1268238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0879 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378030.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC78	NM_001378030.1	MANE Select	c.1302-59G>A	intron	N/A	NP_001364959.1	H3BLT8
CCDC78	NM_001031737.3		c.1298-59G>A	intron	N/A	NP_001026907.2	A2IDD5-1
CCDC78	NM_001378031.1		c.1122-59G>A	intron	N/A	NP_001364960.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC78	ENST00000345165.10	TSL:5 MANE Select	c.1302-59G>A	intron	N/A	ENSP00000316851.5	H3BLT8
CCDC78	ENST00000293889.10	TSL:1	c.1298-59G>A	intron	N/A	ENSP00000293889.6	A2IDD5-1
CCDC78	ENST00000947033.1		c.1302-23G>A	intron	N/A	ENSP00000617092.1

Frequencies

GnomAD3 genomes

AF:

0.0260

AC:

3954

AN:

152182

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0905

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.00673

AC:

1673

AN:

248478

AF XY:

0.00468

show subpopulations

Gnomad AFR exome

AF:

0.0928

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0000473

Gnomad NFE exome

AF:

0.000224

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00273

AC:

3979

AN:

1455172

Hom.:

153

Cov.:

AF XY:

0.00235

AC XY:

1700

AN XY:

723708

show subpopulations

African (AFR)

AF:

0.0959

AC:

3199

AN:

33374

American (AMR)

AF:

0.00412

AC:

184

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39622

South Asian (SAS)

AF:

0.000209

AC:

AN:

86144

European-Finnish (FIN)

AF:

0.0000388

AC:

AN:

51594

Middle Eastern (MID)

AF:

0.00608

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000131

AC:

145

AN:

1107824

Other (OTH)

AF:

0.00657

AC:

395

AN:

60140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

234

468

702

936

1170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0260

AC:

3957

AN:

152300

Hom.:

174

Cov.:

AF XY:

0.0242

AC XY:

1802

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0904

AC:

3754

AN:

41548

American (AMR)

AF:

0.00856

AC:

131

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68028

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

193

386

580

773

966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.0289

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.0

(source)

DANN

Benign

0.43

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over