rs72849388

chr17-80097197-C-T

Variant summary

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

The NM_017950.4(CCDC40):c.3022-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,606,962 control chromosomes in the GnomAD database, including 18,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2760 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15878 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.40

Genes affected

CCDC40 (HGNC:26090): (coiled-coil domain 40 molecular ruler complex subunit) This gene encodes a protein that is necessary for motile cilia function. It functions in correct left-right axis formation by regulating the assembly of the inner dynein arm and the dynein regulatory complexes, which control ciliary beat. Mutations in this gene cause ciliary dyskinesia type 15, a disorder due to defects in cilia motility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-80097197-C-T is Benign according to our data. Variant chr17-80097197-C-T is described in ClinVar as [Benign]. Clinvar id is 260968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.3022-48C>T		intron_variant		ENST00000397545.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.3022-48C>T		intron_variant		5	NM_017950.4	P2
CCDC40	ENST00000574799.5	n.2559-48C>T		intron_variant, non_coding_transcript_variant		1
CCDC40	ENST00000572253.5	n.3273-48C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26900 AN: 152116 Hom.: 2755 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.141 AC: 34916 AN: 248038 Hom.: 2991 AF XY: 0.143 AC XY: 19262 AN XY: 134794

Gnomad AFR exome AF: 0.287

Gnomad AMR exome AF: 0.0848

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.000669

Gnomad SAS exome AF: 0.141

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.141 AC: 205796 AN: 1454728 Hom.: 15878 Cov.: 29 AF XY: 0.142 AC XY: 102646 AN XY: 724018

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.0911

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.000580

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.177 AC: 26915 AN: 152234 Hom.: 2760 Cov.: 33 AF XY: 0.175 AC XY: 13018 AN XY: 74432

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.166

Alfa AF: 0.163 Hom.: 397

Bravo AF: 0.176

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Primary ciliary dyskinesia 15 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.14
Dann	Benign	0.64

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

Other links and lift over

dbSNP: rs72849388; hg19: chr17-78070996;