17-80097253-T-C

Variant names:

• chr17-80097253-T-C
• rs12952612
• NM_017950.4:c.3030T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017950.4(CCDC40):​c.3030T>C​(p.Asp1010Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,613,562 control chromosomes in the GnomAD database, including 444,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (39753 hom., cov: 32)
  • Exomes 𝑓: 0.74 (404429 hom.)
• Consequence: CCDC40 NM_017950.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.368
• Publications: 29 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-80097253-T-C is Benign according to our data. Variant chr17-80097253-T-C is described in ClinVar as Benign. ClinVar VariationId is 178711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.368 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.794 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.3030T>C	p.Asp1010Asp	synonymous	Exon 19 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.3030T>C	p.Asp1010Asp	synonymous	Exon 19 of 20	ENSP00000380679.4	Q4G0X9-1
	CCDC40	ENST00000574799.5	TSL:1	n.2567T>C		non_coding_transcript_exon	Exon 15 of 16
	CCDC40	ENST00000897784.1		c.3222T>C	p.Asp1074Asp	synonymous	Exon 20 of 21	ENSP00000567843.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109475 AN: 151982 Hom.: 39737 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.707

GnomAD2 exomes AF: 0.722 AC: 180181 AN: 249404 AF XY: 0.738

Gnomad AFR exome AF: 0.693

Gnomad AMR exome AF: 0.517

Gnomad ASJ exome AF: 0.798

Gnomad EAS exome AF: 0.633

Gnomad FIN exome AF: 0.797

Gnomad NFE exome AF: 0.755

Gnomad OTH exome AF: 0.755

GnomAD4 exome AF: 0.742 AC: 1084848 AN: 1461462 Hom.: 404429 Cov.: 53 AF XY: 0.746 AC XY: 542238 AN XY: 727046

African (AFR) AF: 0.695 AC: 23279 AN: 33476

American (AMR) AF: 0.528 AC: 23599 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 20918 AN: 26136

East Asian (EAS) AF: 0.696 AC: 27620 AN: 39696

South Asian (SAS) AF: 0.814 AC: 70180 AN: 86256

European-Finnish (FIN) AF: 0.797 AC: 42360 AN: 53168

Middle Eastern (MID) AF: 0.818 AC: 4721 AN: 5768

European-Non Finnish (NFE) AF: 0.744 AC: 826956 AN: 1111850

Other (OTH) AF: 0.749 AC: 45215 AN: 60390

GnomAD4 genome AF: 0.720 AC: 109530 AN: 152100 Hom.: 39753 Cov.: 32 AF XY: 0.719 AC XY: 53476 AN XY: 74366

African (AFR) AF: 0.690 AC: 28634 AN: 41480

American (AMR) AF: 0.589 AC: 9008 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2729 AN: 3472

East Asian (EAS) AF: 0.647 AC: 3349 AN: 5176

South Asian (SAS) AF: 0.816 AC: 3931 AN: 4820

European-Finnish (FIN) AF: 0.809 AC: 8571 AN: 10600

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 50973 AN: 67948

Other (OTH) AF: 0.707 AC: 1491 AN: 2110

Alfa AF: 0.740 Hom.: 86886

Bravo AF: 0.702

Asia WGS AF: 0.732 AC: 2547 AN: 3478

EpiCase AF: 0.752

EpiControl AF: 0.754

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.7
DANN	Benign	0.26
PhyloP100		-0.37
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs12952612; hg19: chr17-78071052; COSMIC: COSV56408680; COSMIC: COSV56408680;