rs3764438

Variant names:

• chr17-80038043-G-A
• rs3764438
• NM_017950.4:c.30-80G>A

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.30-80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 887,852 control chromosomes in the GnomAD database, including 7,893 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1281 hom., cov: 31)
  • Exomes 𝑓: 0.13 (6612 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.733
• Publications: 23 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=-0.92).
• BP6: Variant 17-80038043-G-A is Benign according to our data. Variant chr17-80038043-G-A is described in ClinVar as [Benign]. Clinvar id is 1281104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.30-80G>A		intron_variant	Intron 1 of 19	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.30-80G>A		intron_variant	Intron 1 of 17		NP_001230271.1
CCDC40	NM_001330508.2	c.30-80G>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.30-80G>A		intron_variant	Intron 1 of 19	5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19101 AN: 151962 Hom.: 1283 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.129 AC: 95108 AN: 735770 Hom.: 6612 Cov.: 10 AF XY: 0.130 AC XY: 50678 AN XY: 389552

African (AFR) AF: 0.119 AC: 2274 AN: 19154

American (AMR) AF: 0.0669 AC: 2590 AN: 38694

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 2527 AN: 20548

East Asian (EAS) AF: 0.182 AC: 6244 AN: 34268

South Asian (SAS) AF: 0.130 AC: 8887 AN: 68278

European-Finnish (FIN) AF: 0.167 AC: 8106 AN: 48538

Middle Eastern (MID) AF: 0.140 AC: 514 AN: 3680

European-Non Finnish (NFE) AF: 0.127 AC: 59512 AN: 467192

Other (OTH) AF: 0.126 AC: 4454 AN: 35418

GnomAD4 genome AF: 0.126 AC: 19099 AN: 152082 Hom.: 1281 Cov.: 31 AF XY: 0.127 AC XY: 9419 AN XY: 74354

African (AFR) AF: 0.120 AC: 4979 AN: 41464

American (AMR) AF: 0.0770 AC: 1178 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3472

East Asian (EAS) AF: 0.164 AC: 847 AN: 5158

South Asian (SAS) AF: 0.115 AC: 556 AN: 4822

European-Finnish (FIN) AF: 0.163 AC: 1723 AN: 10566

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9043 AN: 67990

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.125 Hom.: 2441

Bravo AF: 0.117

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.33
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3764438; hg19: chr17-78011842; COSMIC: COSV53898078; COSMIC: COSV53898078;