rs59252872

Variant names:

• chr17-80097448-A-G
• rs59252872
• NM_017950.4:c.3180+45A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-80097448-A-G
• chr17-80097448-A-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.3180+45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,606,880 control chromosomes in the GnomAD database, including 58,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8528 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50288 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.249
• Publications: 7 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=-0.92).
• BP6: Variant 17-80097448-A-G is Benign according to our data. Variant chr17-80097448-A-G is described in ClinVar as Benign. ClinVar VariationId is 260972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 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.3180+45A>G		intron	N/A	NP_060420.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.3180+45A>G		intron	N/A	ENSP00000380679.4	Q4G0X9-1
	CCDC40	ENST00000574799.5	TSL:1	n.2717+45A>G		intron	N/A
	CCDC40	ENST00000897784.1		c.3372+45A>G		intron	N/A	ENSP00000567843.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48059 AN: 151850 Hom.: 8509 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.285

GnomAD2 exomes AF: 0.265 AC: 64650 AN: 244122 AF XY: 0.267

Gnomad AFR exome AF: 0.493

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.235

Gnomad EAS exome AF: 0.284

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.272

GnomAD4 exome AF: 0.258 AC: 375695 AN: 1454912 Hom.: 50288 Cov.: 30 AF XY: 0.259 AC XY: 187242 AN XY: 723598

African (AFR) AF: 0.494 AC: 16474 AN: 33356

American (AMR) AF: 0.151 AC: 6736 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 6174 AN: 26058

East Asian (EAS) AF: 0.314 AC: 12420 AN: 39576

South Asian (SAS) AF: 0.276 AC: 23745 AN: 86026

European-Finnish (FIN) AF: 0.298 AC: 15713 AN: 52772

Middle Eastern (MID) AF: 0.270 AC: 1555 AN: 5758

European-Non Finnish (NFE) AF: 0.250 AC: 276659 AN: 1106748

Other (OTH) AF: 0.270 AC: 16219 AN: 60128

GnomAD4 genome AF: 0.317 AC: 48122 AN: 151968 Hom.: 8528 Cov.: 32 AF XY: 0.313 AC XY: 23280 AN XY: 74296

African (AFR) AF: 0.485 AC: 20087 AN: 41424

American (AMR) AF: 0.188 AC: 2877 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 789 AN: 3468

East Asian (EAS) AF: 0.295 AC: 1513 AN: 5128

South Asian (SAS) AF: 0.268 AC: 1291 AN: 4810

European-Finnish (FIN) AF: 0.292 AC: 3088 AN: 10584

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17473 AN: 67954

Other (OTH) AF: 0.288 AC: 607 AN: 2110

Alfa AF: 0.280 Hom.: 1197

Bravo AF: 0.318

Asia WGS AF: 0.309 AC: 1077 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 15 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.31
PhyloP100		0.25
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: rs59252872; hg19: chr17-78071247; COSMIC: COSV56408175; COSMIC: COSV56408175;