NM_017950.4:c.*15T>C

Variant names:

• chr17-80099790-T-C
• rs2304853
• NM_017950.4:c.*15T>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.*15T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,610,396 control chromosomes in the GnomAD database, including 73,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10337 hom., cov: 32)
  • Exomes 𝑓: 0.29 (63205 hom.)
• Consequence: CCDC40 NM_017950.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.649
• Publications: 13 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=-0.88).
• BP6: Variant 17-80099790-T-C is Benign according to our data. Variant chr17-80099790-T-C is described in ClinVar as Benign. ClinVar VariationId is 162853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 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.*15T>C		3_prime_UTR	Exon 20 of 20	NP_060420.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.*15T>C		3_prime_UTR	Exon 20 of 20	ENSP00000380679.4	Q4G0X9-1
	CCDC40	ENST00000574799.5	TSL:1	n.2981T>C		non_coding_transcript_exon	Exon 16 of 16
	CCDC40	ENST00000897784.1		c.*15T>C		3_prime_UTR	Exon 21 of 21	ENSP00000567843.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53366 AN: 151808 Hom.: 10320 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.328

GnomAD2 exomes AF: 0.302 AC: 73977 AN: 245030 AF XY: 0.305

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.409

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.289

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.288 AC: 420697 AN: 1458470 Hom.: 63205 Cov.: 35 AF XY: 0.290 AC XY: 210262 AN XY: 725646

African (AFR) AF: 0.525 AC: 17556 AN: 33416

American (AMR) AF: 0.171 AC: 7624 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 6984 AN: 26094

East Asian (EAS) AF: 0.453 AC: 17967 AN: 39664

South Asian (SAS) AF: 0.325 AC: 28004 AN: 86184

European-Finnish (FIN) AF: 0.340 AC: 17527 AN: 51604

Middle Eastern (MID) AF: 0.302 AC: 1743 AN: 5764

European-Non Finnish (NFE) AF: 0.274 AC: 304774 AN: 1110800

Other (OTH) AF: 0.307 AC: 18518 AN: 60308

GnomAD4 genome AF: 0.352 AC: 53424 AN: 151926 Hom.: 10337 Cov.: 32 AF XY: 0.350 AC XY: 26005 AN XY: 74278

African (AFR) AF: 0.516 AC: 21370 AN: 41384

American (AMR) AF: 0.216 AC: 3294 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 889 AN: 3462

East Asian (EAS) AF: 0.424 AC: 2185 AN: 5150

South Asian (SAS) AF: 0.327 AC: 1579 AN: 4824

European-Finnish (FIN) AF: 0.333 AC: 3526 AN: 10574

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19467 AN: 67940

Other (OTH) AF: 0.332 AC: 699 AN: 2108

Alfa AF: 0.303 Hom.: 3763

Bravo AF: 0.350

Asia WGS AF: 0.387 AC: 1350 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Primary ciliary dyskinesia 15 (3)
-	-	2	not provided (2)
-	-	1	Glycogen storage disease, type II (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.41
PhyloP100		-0.65
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: rs2304853; hg19: chr17-78073589; COSMIC: COSV56408051; COSMIC: COSV56408051;