10-13093046-T-C

Position:

• chr10-13093046-T-C

Variant summary

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

The NM_001282658.2(CCDC3):​c.-503+5479A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 135,740 control chromosomes in the GnomAD database, including 13,280 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 0.46 (13280 hom., cov: 24)
• Consequence: CCDC3 NM_001282658.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC3	NM_001282658.2	c.-503+5479A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC3	ENST00000378839.1	c.-503+5479A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 61845 AN: 135712 Hom.: 13290 Cov.: 24

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.575

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.455 AC: 61818 AN: 135740 Hom.: 13280 Cov.: 24 AF XY: 0.447 AC XY: 29283 AN XY: 65544

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.517

Alfa AF: 0.445 Hom.: 6590

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.19
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10796021; hg19: chr10-13135046;