10-12974528-C-G

Variant names:

• chr10-12974528-C-G
• rs2248161
• NM_031455.4:c.549+23810G>C

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.87).
• 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 rank	MANE	Protein	UniProt
CCDC3	NM_031455.4	c.549+23810G>C		intron_variant	Intron 2 of 2	ENST00000378825.5	NP_113643.1
CCDC3	NM_001282658.2	c.174+23810G>C		intron_variant	Intron 6 of 6		NP_001269587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC3	ENST00000378825.5	c.549+23810G>C		intron_variant	Intron 2 of 2	1	NM_031455.4	ENSP00000368102.3
CCDC3	ENST00000378839.1	c.174+23810G>C		intron_variant	Intron 6 of 6	2		ENSP00000368116.1

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

African (AFR) AF: 0.573 AC: 23775 AN: 41468

American (AMR) AF: 0.575 AC: 8796 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3468

East Asian (EAS) AF: 0.484 AC: 2487 AN: 5142

South Asian (SAS) AF: 0.650 AC: 3133 AN: 4820

European-Finnish (FIN) AF: 0.574 AC: 6073 AN: 10574

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38445 AN: 67998

Other (OTH) AF: 0.536 AC: 1133 AN: 2112

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
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2248161; hg19: chr10-13016528;