rs8079308

Positions:

• chr17-44902821-G-A
• chr17-44902821-G-C
• chr17-44902821-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_213607.3(CCDC103):​c.*4G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,533,062 control chromosomes in the GnomAD database, including 56,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5267 hom., cov: 31)
  • Exomes 𝑓: 0.27 (51592 hom.)
• Consequence: CCDC103 NM_213607.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.198

Genes affected

CCDC103 (HGNC:32700): (coiled-coil domain containing 103) Enables protein homodimerization activity. Involved in axonemal dynein complex assembly; cilium movement; and determination of left/right symmetry. Predicted to be located in axoneme. Predicted to be part of outer dynein arm. Implicated in primary ciliary dyskinesia 17. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-44902821-G-A is Benign according to our data. Variant chr17-44902821-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 263317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-44902821-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC103	NM_213607.3	c.*4G>A		3_prime_UTR_variant	4/4	ENST00000417826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC103	ENST00000417826.3	c.*4G>A		3_prime_UTR_variant	4/4	1	NM_213607.3	P1
CCDC103	ENST00000410006.6	c.*4G>A		3_prime_UTR_variant	4/4	2		P1
CCDC103	ENST00000357776.6			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39674 AN: 151720 Hom.: 5262 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.264

GnomAD3 exomes AF: 0.271 AC: 40562 AN: 149542 Hom.: 5607 AF XY: 0.271 AC XY: 21424 AN XY: 78986

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.262

Gnomad SAS exome AF: 0.288

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.273 AC: 376894 AN: 1381224 Hom.: 51592 Cov.: 36 AF XY: 0.273 AC XY: 185576 AN XY: 678538

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.261 AC: 39701 AN: 151838 Hom.: 5267 Cov.: 31 AF XY: 0.261 AC XY: 19365 AN XY: 74176

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.262

Alfa AF: 0.247 Hom.: 2147

Bravo AF: 0.253

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Primary ciliary dyskinesia 17 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs8079308; hg19: chr17-42980189; COSMIC: COSV53654651; COSMIC: COSV53654651;