rs10083858

Variant names:

• chr17-80065639-G-A
• rs10083858
• NM_017950.4:c.1562+33G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017950.4(CCDC40):​c.1562+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,610,092 control chromosomes in the GnomAD database, including 1,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (803 hom., cov: 30)
  • Exomes 𝑓: 0.0067 (734 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.15
• Publications: 0 publications found

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]

CCDC40 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 15

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autoimmune disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000289689 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-80065639-G-A is Benign according to our data. Variant chr17-80065639-G-A is described in ClinVar as Benign. ClinVar VariationId is 260954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017950.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	NM_017950.4	MANE Select	c.1562+33G>A		intron	N/A	NP_060420.2
	CCDC40	NM_001243342.2		c.1562+33G>A		intron	N/A	NP_001230271.1
	CCDC40	NM_001330508.2		c.1562+33G>A		intron	N/A	NP_001317437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.1562+33G>A		intron	N/A	ENSP00000380679.4
	CCDC40	ENST00000374876.4	TSL:1	c.1318-444G>A		intron	N/A	ENSP00000364010.4
	CCDC40	ENST00000574799.5	TSL:1	n.1099+33G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0585 AC: 8903 AN: 152174 Hom.: 804 Cov.: 30

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.0465

GnomAD2 exomes AF: 0.0156 AC: 3786 AN: 242208 AF XY: 0.0122

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000484

Gnomad NFE exome AF: 0.00153

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00669 AC: 9756 AN: 1457802 Hom.: 734 Cov.: 32 AF XY: 0.00591 AC XY: 4286 AN XY: 725254

African (AFR) AF: 0.202 AC: 6732 AN: 33404

American (AMR) AF: 0.0145 AC: 647 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 241 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000314 AC: 27 AN: 86012

European-Finnish (FIN) AF: 0.0000580 AC: 3 AN: 51694

Middle Eastern (MID) AF: 0.0161 AC: 72 AN: 4472

European-Non Finnish (NFE) AF: 0.00105 AC: 1164 AN: 1111566

Other (OTH) AF: 0.0145 AC: 870 AN: 60190

GnomAD4 genome AF: 0.0585 AC: 8915 AN: 152290 Hom.: 803 Cov.: 30 AF XY: 0.0568 AC XY: 4227 AN XY: 74456

African (AFR) AF: 0.198 AC: 8241 AN: 41548

American (AMR) AF: 0.0287 AC: 439 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00135 AC: 92 AN: 68036

Other (OTH) AF: 0.0460 AC: 97 AN: 2108

Alfa AF: 0.0319 Hom.: 120

Bravo AF: 0.0664

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.27
DANN	Benign	0.86
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10083858; hg19: chr17-78039438;