10-12249577-A-G

Variant names:

• chr10-12249577-A-G
• rs140282256
• NM_006023.3:c.847-4A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006023.3(CDC123):​c.847-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,609,052 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (14 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (179 hom.)
• Consequence: CDC123 NM_006023.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001357
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.406
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 10-12249577-A-G is Benign according to our data. Variant chr10-12249577-A-G is described in ClinVar as Benign. ClinVar VariationId is 779930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006023.3. 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
	CDC123	NM_006023.3	MANE Select	c.847-4A>G		splice_region intron	N/A	NP_006014.2	O75794

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC123	ENST00000281141.9	TSL:1 MANE Select	c.847-4A>G		splice_region intron	N/A	ENSP00000281141.4	O75794
	CDC123	ENST00000932716.1		c.967-4A>G		splice_region intron	N/A	ENSP00000602775.1
	CDC123	ENST00000932723.1		c.946-4A>G		splice_region intron	N/A	ENSP00000602782.1

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 403 AN: 152172 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.0602

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00884 AC: 2178 AN: 246434 AF XY: 0.0111

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.0000911

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.0239

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.00331

GnomAD4 exome AF: 0.00416 AC: 6060 AN: 1456762 Hom.: 179 Cov.: 30 AF XY: 0.00565 AC XY: 4098 AN XY: 724736

African (AFR) AF: 0.000181 AC: 6 AN: 33068

American (AMR) AF: 0.0000932 AC: 4 AN: 42932

Ashkenazi Jewish (ASJ) AF: 0.0000772 AC: 2 AN: 25902

East Asian (EAS) AF: 0.0229 AC: 907 AN: 39674

South Asian (SAS) AF: 0.0557 AC: 4745 AN: 85160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00279 AC: 16 AN: 5740

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1110680

Other (OTH) AF: 0.00538 AC: 324 AN: 60212

GnomAD4 genome AF: 0.00264 AC: 402 AN: 152290 Hom.: 14 Cov.: 33 AF XY: 0.00400 AC XY: 298 AN XY: 74466

African (AFR) AF: 0.0000481 AC: 2 AN: 41550

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0183 AC: 95 AN: 5182

South Asian (SAS) AF: 0.0600 AC: 290 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68024

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.000343 Hom.: 0

Bravo AF: 0.00130

EpiCase AF: 0.000327

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.1
DANN	Benign	0.67
PhyloP100		0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0
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: rs140282256; hg19: chr10-12291576;