chr16-725947-G-C

Variant names:

• chr16-725947-G-C
• rs12446058
• NM_001378030.1:c.180+19C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.902
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC78	NM_001378030.1	MANE Select	c.180+19C>G		intron	N/A	NP_001364959.1	H3BLT8
	CCDC78	NM_001031737.3		c.180+19C>G		intron	N/A	NP_001026907.2	A2IDD5-1
	CCDC78	NM_001378031.1		c.180+19C>G		intron	N/A	NP_001364960.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC78	ENST00000345165.10	TSL:5 MANE Select	c.180+19C>G		intron	N/A	ENSP00000316851.5	H3BLT8
	CCDC78	ENST00000293889.10	TSL:1	c.180+19C>G		intron	N/A	ENSP00000293889.6	A2IDD5-1
	CCDC78	ENST00000947033.1		c.180+19C>G		intron	N/A	ENSP00000617092.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30069 AN: 151904 Hom.: 3366 Cov.: 33

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

GnomAD2 exomes AF: 0.212 AC: 36866 AN: 173960 AF XY: 0.224

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 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.: 38 AF XY: 0.242 AC XY: 169058 AN XY: 698392

African (AFR) AF: 0.122 AC: 3927 AN: 32272

American (AMR) AF: 0.111 AC: 4182 AN: 37656

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 4550 AN: 25394

East Asian (EAS) AF: 0.0221 AC: 818 AN: 37070

South Asian (SAS) AF: 0.320 AC: 26018 AN: 81390

European-Finnish (FIN) AF: 0.265 AC: 12851 AN: 48476

Middle Eastern (MID) AF: 0.154 AC: 880 AN: 5714

European-Non Finnish (NFE) AF: 0.250 AC: 271532 AN: 1085776

Other (OTH) AF: 0.216 AC: 12633 AN: 58456

GnomAD4 genome AF: 0.198 AC: 30100 AN: 152022 Hom.: 3372 Cov.: 33 AF XY: 0.199 AC XY: 14796 AN XY: 74318

African (AFR) AF: 0.126 AC: 5250 AN: 41520

American (AMR) AF: 0.153 AC: 2339 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3468

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5184

South Asian (SAS) AF: 0.317 AC: 1524 AN: 4810

European-Finnish (FIN) AF: 0.258 AC: 2727 AN: 10578

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16871 AN: 67868

Other (OTH) AF: 0.184 AC: 387 AN: 2108

Alfa AF: 0.152 Hom.: 466

Bravo AF: 0.181

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital myopathy with internal nuclei and atypical cores (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.26
PhyloP100		-0.90
PromoterAI		-0.0028	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12446058; hg19: chr16-775947; COSMIC: COSV52402257; COSMIC: COSV52402257;