NM_001282658.2:c.-1-6994C>T

Variant names:

• chr10-13005506-G-A
• rs552437
• NM_001282658.2:c.-1-6994C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282658.2(CCDC3):​c.-1-6994C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,124 control chromosomes in the GnomAD database, including 50,869 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 0.81 (50869 hom., cov: 31)
• Consequence: CCDC3 NM_001282658.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC3	NM_001282658.2	c.-1-6994C>T		intron_variant	Intron 5 of 6		NP_001269587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC3	ENST00000378839.1	c.-1-6994C>T		intron_variant	Intron 5 of 6	2		ENSP00000368116.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122989 AN: 152006 Hom.: 50825 Cov.: 31

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.809 AC: 123085 AN: 152124 Hom.: 50869 Cov.: 31 AF XY: 0.808 AC XY: 60107 AN XY: 74402

African (AFR) AF: 0.632 AC: 26207 AN: 41452

American (AMR) AF: 0.867 AC: 13261 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2904 AN: 3470

East Asian (EAS) AF: 0.834 AC: 4308 AN: 5168

South Asian (SAS) AF: 0.758 AC: 3657 AN: 4824

European-Finnish (FIN) AF: 0.904 AC: 9578 AN: 10594

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60312 AN: 68012

Other (OTH) AF: 0.831 AC: 1756 AN: 2112

Alfa AF: 0.863 Hom.: 28811

Bravo AF: 0.801

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.29
DANN	Benign	0.61
PhyloP100		-1.9
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: rs552437; hg19: chr10-13047506;