10-12225655-A-G

Variant names:

• chr10-12225655-A-G
• rs4478891
• NM_006023.3:c.441-5293A>G

Variant summary

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

The NM_006023.3(CDC123):​c.441-5293A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 150,742 control chromosomes in the GnomAD database, including 20,715 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 0.52 (20715 hom., cov: 28)
• Consequence: CDC123 NM_006023.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490
• Publications: 7 publications found

Genes affected

CDC123 (HGNC:16827): (cell division cycle 123) Predicted to be involved in eukaryotic translation initiation factor 2 complex assembly and positive regulation of translational initiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000228302 (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 (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC123	NM_006023.3	c.441-5293A>G		intron_variant	Intron 6 of 12	ENST00000281141.9	NP_006014.2
CDC123	XM_005252638.5	c.345-5293A>G		intron_variant	Intron 5 of 11		XP_005252695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC123	ENST00000281141.9	c.441-5293A>G		intron_variant	Intron 6 of 12	1	NM_006023.3	ENSP00000281141.4

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78091 AN: 150630 Hom.: 20704 Cov.: 28

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.518 AC: 78132 AN: 150742 Hom.: 20715 Cov.: 28 AF XY: 0.518 AC XY: 38109 AN XY: 73566

African (AFR) AF: 0.398 AC: 16243 AN: 40858

American (AMR) AF: 0.574 AC: 8701 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1942 AN: 3468

East Asian (EAS) AF: 0.421 AC: 2137 AN: 5078

South Asian (SAS) AF: 0.550 AC: 2624 AN: 4774

European-Finnish (FIN) AF: 0.527 AC: 5407 AN: 10268

Middle Eastern (MID) AF: 0.638 AC: 185 AN: 290

European-Non Finnish (NFE) AF: 0.576 AC: 39088 AN: 67844

Other (OTH) AF: 0.563 AC: 1183 AN: 2100

Alfa AF: 0.554 Hom.: 16423

Bravo AF: 0.515

Asia WGS AF: 0.521 AC: 1811 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.40
DANN	Benign	0.50
PhyloP100		-0.49
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: rs4478891; hg19: chr10-12267654;