10-12974528-C-G

Variant summary

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

The NM_031455.4(CCDC3):c.549+23810G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,084 control chromosomes in the GnomAD database, including 24,599 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 0.57 (24599 hom., cov: 33)
• Consequence: CCDC3 NM_031455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC3	NM_031455.4	c.549+23810G>C		intron_variant		ENST00000378825.5
CCDC3	NM_001282658.2	c.174+23810G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC3	ENST00000378825.5	c.549+23810G>C		intron_variant		1	NM_031455.4	P1
CCDC3	ENST00000378839.1	c.174+23810G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86387 AN: 151966 Hom.: 24575 Cov.: 33

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.569 AC: 86462 AN: 152084 Hom.: 24599 Cov.: 33 AF XY: 0.570 AC XY: 42399 AN XY: 74326

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.536

Alfa AF: 0.466 Hom.: 1373

Bravo AF: 0.566

Asia WGS AF: 0.579 AC: 2015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	9.5
Dann	Benign	0.27

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: rs2248161; hg19: chr10-13016528;