rs11257600

Positions:

• chr10-12213658-G-T

Variant summary

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

The NM_006023.3(CDC123):​c.238-2082G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,748 control chromosomes in the GnomAD database, including 5,973 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 0.27 (5973 hom., cov: 32)
• Consequence: CDC123 NM_006023.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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

Verdict is Benign. Variant got -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 = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC123	NM_006023.3	c.238-2082G>T		intron_variant		ENST00000281141.9
CDC123	XM_005252638.5	c.237+3336G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC123	ENST00000281141.9	c.238-2082G>T		intron_variant		1	NM_006023.3	P1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41428 AN: 151634 Hom.: 5972 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.273 AC: 41442 AN: 151748 Hom.: 5973 Cov.: 32 AF XY: 0.275 AC XY: 20398 AN XY: 74158

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.259

Alfa AF: 0.255 Hom.: 1015

Bravo AF: 0.275

Asia WGS AF: 0.344 AC: 1194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs11257600; hg19: chr10-12255657;