chr17-80037892-A-G

Variant names:

• chr17-80037892-A-G
• rs3764440
• NM_017950.4:c.30-231A>G

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.30-231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 438,924 control chromosomes in the GnomAD database, including 15,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7244 hom., cov: 29)
  • Exomes 𝑓: 0.23 (8075 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.686
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-80037892-A-G is Benign according to our data. Variant chr17-80037892-A-G is described in ClinVar as [Benign]. Clinvar id is 1262578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.30-231A>G		intron_variant	Intron 1 of 19	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.30-231A>G		intron_variant	Intron 1 of 17		NP_001230271.1
CCDC40	NM_001330508.2	c.30-231A>G		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.30-231A>G		intron_variant	Intron 1 of 19	5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43503 AN: 151202 Hom.: 7243 Cov.: 29

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.230 AC: 66060 AN: 287604 Hom.: 8075 AF XY: 0.227 AC XY: 35119 AN XY: 155022

African (AFR) AF: 0.462 AC: 3682 AN: 7966

American (AMR) AF: 0.147 AC: 2023 AN: 13766

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 1802 AN: 7904

East Asian (EAS) AF: 0.180 AC: 2973 AN: 16496

South Asian (SAS) AF: 0.193 AC: 8261 AN: 42892

European-Finnish (FIN) AF: 0.291 AC: 4705 AN: 16190

Middle Eastern (MID) AF: 0.280 AC: 315 AN: 1124

European-Non Finnish (NFE) AF: 0.233 AC: 38670 AN: 166102

Other (OTH) AF: 0.239 AC: 3629 AN: 15164

GnomAD4 genome AF: 0.288 AC: 43530 AN: 151320 Hom.: 7244 Cov.: 29 AF XY: 0.286 AC XY: 21116 AN XY: 73902

African (AFR) AF: 0.460 AC: 18936 AN: 41180

American (AMR) AF: 0.171 AC: 2591 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3468

East Asian (EAS) AF: 0.165 AC: 846 AN: 5126

South Asian (SAS) AF: 0.170 AC: 818 AN: 4800

European-Finnish (FIN) AF: 0.272 AC: 2832 AN: 10418

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 15976 AN: 67830

Other (OTH) AF: 0.264 AC: 553 AN: 2096

Alfa AF: 0.284 Hom.: 885

Bravo AF: 0.287

Asia WGS AF: 0.183 AC: 638 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.54
DANN	Benign	0.42
PhyloP100		-0.69
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: rs3764440; hg19: chr17-78011691;