rs72849388

Variant names:

• chr17-80097197-C-T
• rs72849388
• NM_017950.4:c.3022-48C>T

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.3022-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,606,962 control chromosomes in the GnomAD database, including 18,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2760 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15878 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.40
• Publications: 4 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
• 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=-0.9).
• BP6: Variant 17-80097197-C-T is Benign according to our data. Variant chr17-80097197-C-T is described in ClinVar as Benign. ClinVar VariationId is 260968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 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.3022-48C>T		intron	N/A	NP_060420.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.3022-48C>T		intron	N/A	ENSP00000380679.4	Q4G0X9-1
	CCDC40	ENST00000574799.5	TSL:1	n.2559-48C>T		intron	N/A
	CCDC40	ENST00000897784.1		c.3214-48C>T		intron	N/A	ENSP00000567843.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26900 AN: 152116 Hom.: 2755 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.168

GnomAD2 exomes AF: 0.141 AC: 34916 AN: 248038 AF XY: 0.143

Gnomad AFR exome AF: 0.287

Gnomad AMR exome AF: 0.0848

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.000669

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.141 AC: 205796 AN: 1454728 Hom.: 15878 Cov.: 29 AF XY: 0.142 AC XY: 102646 AN XY: 724018

African (AFR) AF: 0.289 AC: 9628 AN: 33328

American (AMR) AF: 0.0911 AC: 4071 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3997 AN: 26098

East Asian (EAS) AF: 0.000580 AC: 23 AN: 39676

South Asian (SAS) AF: 0.138 AC: 11883 AN: 86112

European-Finnish (FIN) AF: 0.174 AC: 9131 AN: 52338

Middle Eastern (MID) AF: 0.202 AC: 1160 AN: 5748

European-Non Finnish (NFE) AF: 0.142 AC: 157086 AN: 1106572

Other (OTH) AF: 0.147 AC: 8817 AN: 60150

GnomAD4 genome AF: 0.177 AC: 26915 AN: 152234 Hom.: 2760 Cov.: 33 AF XY: 0.175 AC XY: 13018 AN XY: 74432

African (AFR) AF: 0.283 AC: 11732 AN: 41518

American (AMR) AF: 0.103 AC: 1576 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 522 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.118 AC: 570 AN: 4828

European-Finnish (FIN) AF: 0.172 AC: 1823 AN: 10610

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10138 AN: 68002

Other (OTH) AF: 0.166 AC: 351 AN: 2116

Alfa AF: 0.165 Hom.: 736

Bravo AF: 0.176

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 15 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.64
PhyloP100		-1.4
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs72849388;

hg19: chr17-78070996;