NM_017950.4:c.1159+12C>T

Variant names:

• chr17-80050295-C-T
• rs2289533
• NM_017950.4:c.1159+12C>T

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.1159+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,548,256 control chromosomes in the GnomAD database, including 45,677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3592 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42085 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.684
• Publications: 12 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=-0.8).
• BP6: Variant 17-80050295-C-T is Benign according to our data. Variant chr17-80050295-C-T is described in ClinVar as Benign. ClinVar VariationId is 162847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 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.1159+12C>T		intron	N/A	NP_060420.2
	CCDC40	NM_001243342.2		c.1159+12C>T		intron	N/A	NP_001230271.1
	CCDC40	NM_001330508.2		c.1159+12C>T		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.1159+12C>T		intron	N/A	ENSP00000380679.4
	CCDC40	ENST00000374876.4	TSL:1	c.1159+12C>T		intron	N/A	ENSP00000364010.4
	CCDC40	ENST00000574799.5	TSL:1	n.696+12C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29749 AN: 152010 Hom.: 3587 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.201

GnomAD2 exomes AF: 0.242 AC: 37159 AN: 153680 AF XY: 0.238

Gnomad AFR exome AF: 0.0427

Gnomad AMR exome AF: 0.303

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.402

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.241 AC: 337160 AN: 1396128 Hom.: 42085 Cov.: 33 AF XY: 0.241 AC XY: 166177 AN XY: 689096

African (AFR) AF: 0.0415 AC: 1311 AN: 31572

American (AMR) AF: 0.301 AC: 10778 AN: 35860

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4641 AN: 25188

East Asian (EAS) AF: 0.318 AC: 11382 AN: 35820

South Asian (SAS) AF: 0.207 AC: 16459 AN: 79458

European-Finnish (FIN) AF: 0.221 AC: 10727 AN: 48604

Middle Eastern (MID) AF: 0.171 AC: 694 AN: 4066

European-Non Finnish (NFE) AF: 0.249 AC: 267915 AN: 1077734

Other (OTH) AF: 0.229 AC: 13253 AN: 57826

GnomAD4 genome AF: 0.196 AC: 29769 AN: 152128 Hom.: 3592 Cov.: 32 AF XY: 0.199 AC XY: 14781 AN XY: 74352

African (AFR) AF: 0.0539 AC: 2238 AN: 41534

American (AMR) AF: 0.293 AC: 4475 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 651 AN: 3466

East Asian (EAS) AF: 0.373 AC: 1925 AN: 5154

South Asian (SAS) AF: 0.212 AC: 1019 AN: 4814

European-Finnish (FIN) AF: 0.218 AC: 2309 AN: 10588

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16466 AN: 67962

Other (OTH) AF: 0.203 AC: 429 AN: 2114

Alfa AF: 0.223 Hom.: 11451

Bravo AF: 0.194

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia 15 (2)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.0
DANN	Benign	0.67
PhyloP100		0.68
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: rs2289533; hg19: chr17-78024094;