chr17-80038204-C-A

Variant names:

• chr17-80038204-C-A
• rs8074956
• NM_017950.4:c.93+18C>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.93+18C>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 1,524,936 control chromosomes in the GnomAD database, including 1,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (800 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (650 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.02
• Publications: 3 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

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

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 17-80038204-C-A is Benign according to our data. Variant chr17-80038204-C-A is described in ClinVar as Benign. ClinVar VariationId is 260981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	NM_017950.4	MANE Select	c.93+18C>A		intron	N/A	NP_060420.2
	CCDC40	NM_001243342.2		c.93+18C>A		intron	N/A	NP_001230271.1	Q4G0X9-2
	CCDC40	NM_001330508.2		c.93+18C>A		intron	N/A	NP_001317437.1	Q4G0X9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.93+18C>A		intron	N/A	ENSP00000380679.4	Q4G0X9-1
	CCDC40	ENST00000374876.4	TSL:1	c.93+18C>A		intron	N/A	ENSP00000364010.4	Q4G0X9-5
	CCDC40	ENST00000897784.1		c.93+18C>A		intron	N/A	ENSP00000567843.1

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8824 AN: 152120 Hom.: 802 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0445

GnomAD2 exomes AF: 0.0155 AC: 3812 AN: 245702 AF XY: 0.0125

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.00254

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000734

Gnomad OTH exome AF: 0.00950

GnomAD4 exome AF: 0.00647 AC: 8887 AN: 1372698 Hom.: 650 Cov.: 21 AF XY: 0.00595 AC XY: 4090 AN XY: 687596

African (AFR) AF: 0.194 AC: 6069 AN: 31236

American (AMR) AF: 0.0127 AC: 560 AN: 44252

Ashkenazi Jewish (ASJ) AF: 0.00229 AC: 58 AN: 25356

East Asian (EAS) AF: 0.00 AC: 0 AN: 39198

South Asian (SAS) AF: 0.00918 AC: 772 AN: 84074

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 53002

Middle Eastern (MID) AF: 0.0106 AC: 59 AN: 5544

European-Non Finnish (NFE) AF: 0.000571 AC: 590 AN: 1032680

Other (OTH) AF: 0.0136 AC: 778 AN: 57356

GnomAD4 genome AF: 0.0580 AC: 8836 AN: 152238 Hom.: 800 Cov.: 32 AF XY: 0.0565 AC XY: 4203 AN XY: 74454

African (AFR) AF: 0.198 AC: 8214 AN: 41498

American (AMR) AF: 0.0274 AC: 419 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00952 AC: 46 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68026

Other (OTH) AF: 0.0440 AC: 93 AN: 2112

Alfa AF: 0.0264 Hom.: 798

Bravo AF: 0.0656

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.094
DANN	Benign	0.59
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8074956; hg19: chr17-78012003;