rs199893871

chr16-724518-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001378030.1(CCDC78):c.766-9C>T 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 0.000788 in 1,592,628 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00083 (25 hom.)
• Consequence: CCDC78 NM_001378030.1 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.001439
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.75

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 16-724518-G-A is Benign according to our data. Variant chr16-724518-G-A is described in ClinVar as [Benign]. Clinvar id is 540477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00083 (1195/1440340) while in subpopulation EAS AF= 0.0298 (1169/39218). AF 95% confidence interval is 0.0284. There are 25 homozygotes in gnomad4_exome. There are 562 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.
• BS2: High AC in GnomAd at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC78	NM_001378030.1	c.766-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000345165.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC78	ENST00000345165.10	c.766-9C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001378030.1	A2

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152170 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000420 AC: 89 AN: 211850 Hom.: 0 AF XY: 0.000448 AC XY: 53 AN XY: 118402

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00498

Gnomad SAS exome AF: 0.000136

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000210

Gnomad OTH exome AF: 0.000185

GnomAD4 exome AF: 0.000830 AC: 1195 AN: 1440340 Hom.: 25 Cov.: 35 AF XY: 0.000784 AC XY: 562 AN XY: 716558

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0298

Gnomad4 SAS exome AF: 0.0000818

Gnomad4 FIN exome AF: 0.0000262

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.000250

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152288 Hom.: 0 Cov.: 34 AF XY: 0.000497 AC XY: 37 AN XY: 74470

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000143 Hom.: 0

Bravo AF: 0.000276

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital myopathy with internal nuclei and atypical cores Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	14
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0014
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs199893871; hg19: chr16-774518;