chr16-722848-C-T

Position:

• chr16-722848-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60

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=-0.91).
• BP6: Variant 16-722848-C-T is Benign according to our data. Variant chr16-722848-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC78	NM_001378030.1	c.1302-59G>A		intron_variant		ENST00000345165.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC78	ENST00000345165.10	c.1302-59G>A		intron_variant		5	NM_001378030.1	A2

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3954 AN: 152182 Hom.: 174 Cov.: 34

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

GnomAD3 exomes AF: 0.00673 AC: 1673 AN: 248478 Hom.: 74 AF XY: 0.00468 AC XY: 631 AN XY: 134962

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 SAS exome AF: 0.000262

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.: 33 AF XY: 0.00235 AC XY: 1700 AN XY: 723708

Gnomad4 AFR exome AF: 0.0959

Gnomad4 AMR exome AF: 0.00412

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.0000388

Gnomad4 NFE exome AF: 0.000131

Gnomad4 OTH exome AF: 0.00657

GnomAD4 genome AF: 0.0260 AC: 3957 AN: 152300 Hom.: 174 Cov.: 34 AF XY: 0.0242 AC XY: 1802 AN XY: 74468

Gnomad4 AFR AF: 0.0904

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00144 Hom.: 0

Bravo AF: 0.0289

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs55652059; hg19: chr16-772848;