17-80036911-C-T

Position:

• chr17-80036911-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.29+220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 152,126 control chromosomes in the GnomAD database, including 452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.069 (452 hom., cov: 31)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0750

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=-0.56).
• BP6: Variant 17-80036911-C-T is Benign according to our data. Variant chr17-80036911-C-T is described in ClinVar as [Benign]. Clinvar id is 1290071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.29+220C>T		intron_variant		ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.29+220C>T		intron_variant			NP_001230271.1
CCDC40	NM_001330508.2	c.29+220C>T		intron_variant			NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.29+220C>T		intron_variant		5	NM_017950.4	ENSP00000380679	P2

Frequencies

GnomAD3 genomes AF: 0.0692 AC: 10526 AN: 152008 Hom.: 453 Cov.: 31

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.0652

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0692 AC: 10525 AN: 152126 Hom.: 452 Cov.: 31 AF XY: 0.0700 AC XY: 5203 AN XY: 74366

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.0448

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.0625

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.0659

Alfa AF: 0.0851 Hom.: 95

Bravo AF: 0.0615

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3752040; hg19: chr17-78010710; COSMIC: COSV53905543; COSMIC: COSV53905543;