rs2580882

chr10-13021108-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282658.2(CCDC3):c.-1-22596C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,232 control chromosomes in the GnomAD database, including 1,423 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1423 hom., cov: 33)
• Consequence: CCDC3 NM_001282658.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

Genes affected

CCDC3 (HGNC:23813): (coiled-coil domain containing 3) Involved in negative regulation of gene expression; negative regulation of lipid metabolic process; and negative regulation of tumor necrosis factor-mediated signaling pathway. Located in endoplasmic reticulum and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC3	NM_001282658.2	c.-1-22596C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC3	ENST00000378839.1	c.-1-22596C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19861 AN: 152114 Hom.: 1422 Cov.: 33

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00846

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 19866 AN: 152232 Hom.: 1423 Cov.: 33 AF XY: 0.130 AC XY: 9645 AN XY: 74432

Gnomad4 AFR AF: 0.0953

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.00829

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.132

Alfa AF: 0.138 Hom.: 178

Bravo AF: 0.128

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2580882; hg19: chr10-13063108;