rs7207441

chr17-80047238-A-G

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.553-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,599,436 control chromosomes in the GnomAD database, including 56,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (11348 hom., cov: 33)
  • Exomes 𝑓: 0.24 (44653 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.17

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=-0.92).
• BP6: Variant 17-80047238-A-G is Benign according to our data. Variant chr17-80047238-A-G is described in ClinVar as [Benign]. Clinvar id is 260976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.553-41A>G		intron_variant		ENST00000397545.9
CCDC40	NM_001243342.2	c.553-41A>G		intron_variant
CCDC40	NM_001330508.2	c.553-41A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.553-41A>G		intron_variant		5	NM_017950.4	P2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51615 AN: 152096 Hom.: 11327 Cov.: 33

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.304

GnomAD3 exomes AF: 0.248 AC: 61491 AN: 247566 Hom.: 9319 AF XY: 0.249 AC XY: 33417 AN XY: 134470

Gnomad AFR exome AF: 0.643

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.163

Gnomad SAS exome AF: 0.261

Gnomad FIN exome AF: 0.280

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.238 AC: 343813 AN: 1447222 Hom.: 44653 Cov.: 30 AF XY: 0.238 AC XY: 171725 AN XY: 720824

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.340 AC: 51688 AN: 152214 Hom.: 11348 Cov.: 33 AF XY: 0.336 AC XY: 25039 AN XY: 74426

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.302

Alfa AF: 0.290 Hom.: 1429

Bravo AF: 0.343

Asia WGS AF: 0.233 AC: 814 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	-0.92
Cadd	Benign	0.052
Dann	Benign	0.41

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: rs7207441; hg19: chr17-78021037;