rs7212525

Variant names:

• chr17-80047415-T-C
• rs7212525
• NM_017950.4:c.676+13T>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.676+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,607,888 control chromosomes in the GnomAD database, including 56,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (11318 hom., cov: 32)
  • Exomes 𝑓: 0.24 (45352 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.10
• Publications: 10 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

ENSG00000289689 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-80047415-T-C is Benign according to our data. Variant chr17-80047415-T-C is described in ClinVar as Benign. ClinVar VariationId is 178707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 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.676+13T>C		intron	N/A	NP_060420.2
	CCDC40	NM_001243342.2		c.676+13T>C		intron	N/A	NP_001230271.1	Q4G0X9-2
	CCDC40	NM_001330508.2		c.676+13T>C		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.676+13T>C		intron	N/A	ENSP00000380679.4	Q4G0X9-1
	CCDC40	ENST00000374876.4	TSL:1	c.676+13T>C		intron	N/A	ENSP00000364010.4	Q4G0X9-5
	CCDC40	ENST00000897784.1		c.676+13T>C		intron	N/A	ENSP00000567843.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51547 AN: 151974 Hom.: 11296 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.303

GnomAD2 exomes AF: 0.246 AC: 58669 AN: 238144 AF XY: 0.247

Gnomad AFR exome AF: 0.640

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.162

Gnomad FIN exome AF: 0.278

Gnomad NFE exome AF: 0.234

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.240 AC: 349238 AN: 1455796 Hom.: 45352 Cov.: 34 AF XY: 0.240 AC XY: 173865 AN XY: 723964

African (AFR) AF: 0.635 AC: 21193 AN: 33384

American (AMR) AF: 0.141 AC: 6249 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 5981 AN: 26010

East Asian (EAS) AF: 0.182 AC: 7220 AN: 39570

South Asian (SAS) AF: 0.255 AC: 21870 AN: 85608

European-Finnish (FIN) AF: 0.284 AC: 14787 AN: 52134

Middle Eastern (MID) AF: 0.274 AC: 1470 AN: 5368

European-Non Finnish (NFE) AF: 0.230 AC: 255386 AN: 1109360

Other (OTH) AF: 0.251 AC: 15082 AN: 60096

GnomAD4 genome AF: 0.339 AC: 51621 AN: 152092 Hom.: 11318 Cov.: 32 AF XY: 0.336 AC XY: 25026 AN XY: 74372

African (AFR) AF: 0.628 AC: 26038 AN: 41484

American (AMR) AF: 0.188 AC: 2876 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3468

East Asian (EAS) AF: 0.165 AC: 853 AN: 5168

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4820

European-Finnish (FIN) AF: 0.275 AC: 2900 AN: 10564

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16156 AN: 67984

Other (OTH) AF: 0.302 AC: 637 AN: 2112

Alfa AF: 0.298 Hom.: 1568

Bravo AF: 0.343

Asia WGS AF: 0.233 AC: 814 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.67
DANN	Benign	0.17
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7212525; hg19: chr17-78021214;