17-80047238-A-G

Variant names:

• chr17-80047238-A-G
• rs7207441
• NM_017950.4:c.553-41A>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.553-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,599,436 control chromosomes in the GnomAD database, including 56,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (11348 hom., cov: 33)
  • Exomes 𝑓: 0.24 (44653 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.17
• Publications: 10 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

ENSG00000289689 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-80047238-A-G is Benign according to our data. Variant chr17-80047238-A-G is described in ClinVar as Benign. ClinVar VariationId is 260976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.553-41A>G		intron_variant	Intron 3 of 19	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.553-41A>G		intron_variant	Intron 3 of 17		NP_001230271.1
CCDC40	NM_001330508.2	c.553-41A>G		intron_variant	Intron 3 of 10		NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.553-41A>G		intron_variant	Intron 3 of 19	5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51615 AN: 152096 Hom.: 11327 Cov.: 33

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.304

GnomAD2 exomes AF: 0.248 AC: 61491 AN: 247566 AF XY: 0.249

Gnomad AFR exome AF: 0.643

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.163

Gnomad FIN exome AF: 0.280

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.238 AC: 343813 AN: 1447222 Hom.: 44653 Cov.: 30 AF XY: 0.238 AC XY: 171725 AN XY: 720824

African (AFR) AF: 0.632 AC: 20665 AN: 32700

American (AMR) AF: 0.141 AC: 6306 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 5992 AN: 26060

East Asian (EAS) AF: 0.182 AC: 7230 AN: 39646

South Asian (SAS) AF: 0.255 AC: 21862 AN: 85846

European-Finnish (FIN) AF: 0.283 AC: 14944 AN: 52742

Middle Eastern (MID) AF: 0.270 AC: 1545 AN: 5732

European-Non Finnish (NFE) AF: 0.228 AC: 250392 AN: 1100018

Other (OTH) AF: 0.249 AC: 14877 AN: 59818

GnomAD4 genome AF: 0.340 AC: 51688 AN: 152214 Hom.: 11348 Cov.: 33 AF XY: 0.336 AC XY: 25039 AN XY: 74426

African (AFR) AF: 0.628 AC: 26077 AN: 41522

American (AMR) AF: 0.188 AC: 2877 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3470

East Asian (EAS) AF: 0.165 AC: 857 AN: 5188

South Asian (SAS) AF: 0.237 AC: 1144 AN: 4828

European-Finnish (FIN) AF: 0.275 AC: 2915 AN: 10602

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16160 AN: 67994

Other (OTH) AF: 0.302 AC: 639 AN: 2114

Alfa AF: 0.298 Hom.: 1568

Bravo AF: 0.343

Asia WGS AF: 0.233 AC: 814 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 15 Benign:1

Jul 14, 2021

Genome-Nilou Lab

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	-0.92
CADD	Benign	0.052
DANN	Benign	0.41
PhyloP100		-1.2
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: rs7207441; hg19: chr17-78021037;