rs4748011

Variant names:

• chr10-12899157-T-C
• rs4748011
• NM_031455.4:c.550-478A>G

Variant summary

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

The NM_031455.4(CCDC3):​c.550-478A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,866 control chromosomes in the GnomAD database, including 5,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association not found (★).

• Frequency: Genomes: 𝑓 0.26 (5623 hom., cov: 31)
• Consequence: CCDC3 NM_031455.4 intron
• Clinical Significance: association not found criteria provided, single submitter O:1
• Conservation: PhyloP100: -0.707
• Publications: 4 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]

ENSG00000285520 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031455.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC3	NM_031455.4	MANE Select	c.550-478A>G		intron	N/A	NP_113643.1	Q9BQI4-1
	CCDC3	NM_001282658.2		c.175-478A>G		intron	N/A	NP_001269587.1	Q9BQI4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC3	ENST00000378825.5	TSL:1 MANE Select	c.550-478A>G		intron	N/A	ENSP00000368102.3	Q9BQI4-1
	CCDC3	ENST00000870347.1		c.550-499A>G		intron	N/A	ENSP00000540406.1
	CCDC3	ENST00000378839.1	TSL:2	c.175-478A>G		intron	N/A	ENSP00000368116.1	Q9BQI4-2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40129 AN: 151750 Hom.: 5619 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.264 AC: 40164 AN: 151866 Hom.: 5623 Cov.: 31 AF XY: 0.270 AC XY: 20044 AN XY: 74194

African (AFR) AF: 0.320 AC: 13238 AN: 41370

American (AMR) AF: 0.215 AC: 3291 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2168 AN: 5126

South Asian (SAS) AF: 0.415 AC: 1991 AN: 4800

European-Finnish (FIN) AF: 0.313 AC: 3300 AN: 10550

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14747 AN: 67962

Other (OTH) AF: 0.238 AC: 500 AN: 2104

Alfa AF: 0.226 Hom.: 6752

Bravo AF: 0.261

Asia WGS AF: 0.417 AC: 1449 AN: 3478

ClinVar

ClinVar submissions

Significance: association not found

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	-	Lip and oral cavity carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.47
DANN	Benign	0.41
PhyloP100		-0.71
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: rs4748011; hg19: chr10-12941157;