Variant 10-12249577-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Variant links:

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]

CDC123 links:

CDC123 (HGNC:):

CDC123 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 779930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-12249577-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC123	NM_006023.3 linkuse as main transcript	c.847-4A>G		splice_region_variant, intron_variant		ENST00000281141.9	NP_006014.2	O75794
CDC123	XM_005252638.5 linkuse as main transcript	c.751-4A>G		splice_region_variant, intron_variant			XP_005252695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC123	ENST00000281141.9 linkuse as main transcript	c.847-4A>G		splice_region_variant, intron_variant		1	NM_006023.3	ENSP00000281141.4		O75794

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

403

AN:

152172

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00884

AC:

2178

AN:

246434

Hom.:

AF XY:

0.0111

AC XY:

1482

AN XY:

133280

show subpopulations

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 SAS exome

AF:

0.0579

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.:

AF XY:

0.00565

AC XY:

4098

AN XY:

724736

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.0000932

Gnomad4 ASJ exome

AF:

0.0000772

Gnomad4 EAS exome

AF:

0.0229

Gnomad4 SAS exome

AF:

0.0557

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.00538

GnomAD4 genome

AF:

0.00264

AC:

402

AN:

152290

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

298

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0183

Gnomad4 SAS

AF:

0.0600

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000343

Hom.:

Bravo

AF:

0.00130

EpiCase

AF:

0.000327

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.1

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over