chr17-80037932-G-A

Variant names:

• chr17-80037932-G-A
• rs3764439
• NM_017950.4:c.30-191G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017950.4(CCDC40):​c.30-191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 397,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.30-191G>A		intron_variant	Intron 1 of 19	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.30-191G>A		intron_variant	Intron 1 of 17		NP_001230271.1
CCDC40	NM_001330508.2	c.30-191G>A		intron_variant	Intron 1 of 10		NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.30-191G>A		intron_variant	Intron 1 of 19	5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000252 AC: 1 AN: 397528 Hom.: 0 Cov.: 3 AF XY: 0.00000467 AC XY: 1 AN XY: 213926

African (AFR) AF: 0.00 AC: 0 AN: 10394

American (AMR) AF: 0.00 AC: 0 AN: 18574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12508

East Asian (EAS) AF: 0.00 AC: 0 AN: 24336

South Asian (SAS) AF: 0.00 AC: 0 AN: 48780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1638

European-Non Finnish (NFE) AF: 0.00000439 AC: 1 AN: 227940

Other (OTH) AF: 0.00 AC: 0 AN: 21410

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.57
PhyloP100		-0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3764439; hg19: chr17-78011731;