rs3752042

Variant names:

• chr17-80036614-C-A
• rs3752042
• NM_017950.4:c.-49C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80036614-C-A
• chr17-80036614-C-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.-49C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,385,998 control chromosomes in the GnomAD database, including 11,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1283 hom., cov: 32)
  • Exomes 𝑓: 0.13 (10426 hom.)
• Consequence: CCDC40 NM_017950.4 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.957
• Publications: 9 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=-0.65).
• BP6: Variant 17-80036614-C-A is Benign according to our data. Variant chr17-80036614-C-A is described in ClinVar as Benign. ClinVar VariationId is 260946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.-49C>A		upstream_gene_variant		ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.-49C>A		upstream_gene_variant			NP_001230271.1
CCDC40	NM_001330508.2	c.-49C>A		upstream_gene_variant			NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.-49C>A		upstream_gene_variant		5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19135 AN: 151972 Hom.: 1285 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0776

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.139 AC: 4042 AN: 28986 AF XY: 0.142

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.0711

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.210

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.128 AC: 157419 AN: 1233918 Hom.: 10426 Cov.: 30 AF XY: 0.128 AC XY: 76841 AN XY: 601464

African (AFR) AF: 0.119 AC: 2960 AN: 24780

American (AMR) AF: 0.0759 AC: 977 AN: 12876

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 2251 AN: 18548

East Asian (EAS) AF: 0.193 AC: 5386 AN: 27948

South Asian (SAS) AF: 0.133 AC: 7487 AN: 56224

European-Finnish (FIN) AF: 0.168 AC: 5040 AN: 29948

Middle Eastern (MID) AF: 0.155 AC: 618 AN: 3994

European-Non Finnish (NFE) AF: 0.125 AC: 126312 AN: 1008778

Other (OTH) AF: 0.126 AC: 6388 AN: 50822

GnomAD4 genome AF: 0.126 AC: 19132 AN: 152080 Hom.: 1283 Cov.: 32 AF XY: 0.127 AC XY: 9435 AN XY: 74344

African (AFR) AF: 0.120 AC: 4981 AN: 41514

American (AMR) AF: 0.0775 AC: 1185 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.165 AC: 846 AN: 5130

South Asian (SAS) AF: 0.115 AC: 551 AN: 4812

European-Finnish (FIN) AF: 0.165 AC: 1743 AN: 10586

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9053 AN: 67954

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.135 Hom.: 312

Bravo AF: 0.117

Asia WGS AF: 0.129 AC: 448 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		0.96
PromoterAI		0.040	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3752042; hg19: chr17-78010413;