rs74000392

chr17-80097217-G-Achr17-80097217-G-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.3022-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,613,222 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (96 hom., cov: 33)
  • Exomes 𝑓: 0.0097 (225 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.587

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=-0.85).
• BP6: Variant 17-80097217-G-A is Benign according to our data. Variant chr17-80097217-G-A is described in ClinVar as [Benign]. Clinvar id is 260967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.3022-28G>A		intron_variant		ENST00000397545.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.3022-28G>A		intron_variant		5	NM_017950.4	P2
CCDC40	ENST00000574799.5	n.2559-28G>A		intron_variant, non_coding_transcript_variant		1
CCDC40	ENST00000572253.5	n.3273-28G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3613 AN: 152170 Hom.: 95 Cov.: 33

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0511

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00550

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.0149 AC: 3722 AN: 249008 Hom.: 76 AF XY: 0.0148 AC XY: 2000 AN XY: 135204

Gnomad AFR exome AF: 0.0690

Gnomad AMR exome AF: 0.00519

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.0475

Gnomad SAS exome AF: 0.0294

Gnomad FIN exome AF: 0.00126

Gnomad NFE exome AF: 0.00542

Gnomad OTH exome AF: 0.0116

GnomAD4 exome AF: 0.00971 AC: 14179 AN: 1460934 Hom.: 225 Cov.: 30 AF XY: 0.0101 AC XY: 7333 AN XY: 726832

Gnomad4 AFR exome AF: 0.0671

Gnomad4 AMR exome AF: 0.00572

Gnomad4 ASJ exome AF: 0.00168

Gnomad4 EAS exome AF: 0.0384

Gnomad4 SAS exome AF: 0.0295

Gnomad4 FIN exome AF: 0.000983

Gnomad4 NFE exome AF: 0.00586

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome AF: 0.0238 AC: 3619 AN: 152288 Hom.: 96 Cov.: 33 AF XY: 0.0235 AC XY: 1752 AN XY: 74466

Gnomad4 AFR AF: 0.0637

Gnomad4 AMR AF: 0.00830

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0514

Gnomad4 SAS AF: 0.0300

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00547

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00351 Hom.: 1

Bravo AF: 0.0265

Asia WGS AF: 0.0450 AC: 159 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.3
Dann	Benign	0.78

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: rs74000392; hg19: chr17-78071016;