17-44899824-G-A

Position:

• chr17-44899824-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_213607.3(CCDC103):​c.-45G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0947 in 152,588 control chromosomes in the GnomAD database, including 756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (751 hom., cov: 31)
  • Exomes 𝑓: 0.12 (5 hom.)
• Consequence: CCDC103 NM_213607.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.229

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 -16 ACMG points.

• BP6: Variant 17-44899824-G-A is Benign according to our data. Variant chr17-44899824-G-A is described in ClinVar as [Benign]. Clinvar id is 323580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC103	NM_213607.3	c.-45G>A		5_prime_UTR_variant	1/4	ENST00000417826.3	NP_998772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC103	ENST00000417826.3	c.-45G>A		5_prime_UTR_variant	1/4	1	NM_213607.3	ENSP00000391692	P1

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14406 AN: 152120 Hom.: 753 Cov.: 31

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0998

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0854

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.123 AC: 43 AN: 350 Hom.: 5 Cov.: 0 AF XY: 0.130 AC XY: 34 AN XY: 262

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.0946 AC: 14406 AN: 152238 Hom.: 751 Cov.: 31 AF XY: 0.0929 AC XY: 6917 AN XY: 74426

Gnomad4 AFR AF: 0.0511

Gnomad4 AMR AF: 0.0996

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0854

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.119

Alfa AF: 0.118 Hom.: 1392

Bravo AF: 0.0941

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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	-0.66
CADD	Benign	11
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.29		Position offset: 5

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

Publications

LitVar

Other links and lift over

dbSNP: rs2277616; hg19: chr17-42977192;