rs525455

Positions:

• chr10-13061285-G-A
• chr10-13061285-G-C
• chr10-13061285-G-T

Variant summary

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

The NM_001282658.2(CCDC3):​c.-269-11344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,066 control chromosomes in the GnomAD database, including 26,416 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 0.58 (26416 hom., cov: 32)
• Consequence: CCDC3 NM_001282658.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC3	NM_001282658.2	c.-269-11344C>T		intron_variant			NP_001269587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC3	ENST00000378839.1	c.-269-11344C>T		intron_variant		2		ENSP00000368116

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88159 AN: 151948 Hom.: 26379 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.580 AC: 88247 AN: 152066 Hom.: 26416 Cov.: 32 AF XY: 0.578 AC XY: 42987 AN XY: 74336

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.547

Alfa AF: 0.527 Hom.: 31625

Bravo AF: 0.597

Asia WGS AF: 0.415 AC: 1443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs525455; hg19: chr10-13103285;