17-80047262-G-C

Variant names:

• chr17-80047262-G-C
• rs7223400
• NM_017950.4:c.553-17G>C

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.553-17G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,100 control chromosomes in the GnomAD database, including 1,112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (511 hom., cov: 33)
  • Exomes 𝑓: 0.0077 (601 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.855
• 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=-0.85).
• BP6: Variant 17-80047262-G-C is Benign according to our data. Variant chr17-80047262-G-C is described in ClinVar as Benign. ClinVar VariationId is 260975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 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.553-17G>C		intron	N/A	NP_060420.2
	CCDC40	NM_001243342.2		c.553-17G>C		intron	N/A	NP_001230271.1
	CCDC40	NM_001330508.2		c.553-17G>C		intron	N/A	NP_001317437.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.553-17G>C		intron	N/A	ENSP00000380679.4
	CCDC40	ENST00000374876.4	TSL:1	c.553-17G>C		intron	N/A	ENSP00000364010.4
	CCDC40	ENST00000897784.1		c.553-17G>C		intron	N/A	ENSP00000567843.1

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6859 AN: 152250 Hom.: 504 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0517

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0330

GnomAD2 exomes AF: 0.0180 AC: 4471 AN: 249010 AF XY: 0.0174

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.00823

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.000445

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000549

Gnomad OTH exome AF: 0.00875

GnomAD4 exome AF: 0.00769 AC: 11237 AN: 1460732 Hom.: 601 Cov.: 32 AF XY: 0.00845 AC XY: 6142 AN XY: 726752

African (AFR) AF: 0.155 AC: 5154 AN: 33358

American (AMR) AF: 0.00908 AC: 406 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26130

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39696

South Asian (SAS) AF: 0.0493 AC: 4247 AN: 86166

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53174

Middle Eastern (MID) AF: 0.00920 AC: 53 AN: 5762

European-Non Finnish (NFE) AF: 0.000411 AC: 457 AN: 1111392

Other (OTH) AF: 0.0149 AC: 902 AN: 60336

GnomAD4 genome AF: 0.0453 AC: 6901 AN: 152368 Hom.: 511 Cov.: 33 AF XY: 0.0445 AC XY: 3314 AN XY: 74512

African (AFR) AF: 0.152 AC: 6328 AN: 41580

American (AMR) AF: 0.0128 AC: 196 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5192

South Asian (SAS) AF: 0.0524 AC: 253 AN: 4832

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: 0.000647 AC: 44 AN: 68032

Other (OTH) AF: 0.0331 AC: 70 AN: 2114

Alfa AF: 0.0206 Hom.: 46

Bravo AF: 0.0496

Asia WGS AF: 0.0460 AC: 158 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)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.33
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs7223400; hg19: chr17-78021061;