rs151335066

chr17-80087801-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017950.4(CCDC40):c.2619+25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,611,466 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (30 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.01

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 17-80087801-G-A is Benign according to our data. Variant chr17-80087801-G-A is described in ClinVar as [Benign]. Clinvar id is 260961.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-80087801-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00136 (207/152320) while in subpopulation EAS AF= 0.0297 (154/5180). AF 95% confidence interval is 0.0259. There are 6 homozygotes in gnomad4. There are 127 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.2619+25G>A		intron_variant		ENST00000397545.9
CCDC40	NM_001243342.2	c.2619+25G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.2619+25G>A		intron_variant		5	NM_017950.4	P2

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 206 AN: 152202 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0297

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00280 AC: 697 AN: 249210 Hom.: 12 AF XY: 0.00267 AC XY: 361 AN XY: 135280

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.000811

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0304

Gnomad SAS exome AF: 0.00127

Gnomad FIN exome AF: 0.00297

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000991

GnomAD4 exome AF: 0.00126 AC: 1845 AN: 1459146 Hom.: 30 Cov.: 33 AF XY: 0.00126 AC XY: 913 AN XY: 726082

Gnomad4 AFR exome AF: 0.0000599

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0353

Gnomad4 SAS exome AF: 0.00128

Gnomad4 FIN exome AF: 0.00264

Gnomad4 NFE exome AF: 0.0000568

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.00136 AC: 207 AN: 152320 Hom.: 6 Cov.: 32 AF XY: 0.00171 AC XY: 127 AN XY: 74486

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0297

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000430 Hom.: 0

Bravo AF: 0.00127

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.87
Dann	Benign	0.88

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: rs151335066; hg19: chr17-78061600;