rs3790623

Positions:

• chr1-37703906-G-A
• chr1-37703906-G-C

Variant summary

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

The NM_001256875.2(CDCA8):​c.584+559G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,908 control chromosomes in the GnomAD database, including 4,386 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 0.23 (4386 hom., cov: 31)
• Consequence: CDCA8 NM_001256875.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91

Genes affected

CDCA8 (HGNC:14629): (cell division cycle associated 8) This gene encodes a component of the chromosomal passenger complex. This complex is an essential regulator of mitosis and cell division. This protein is cell-cycle regulated and is required for chromatin-induced microtubule stabilization and spindle formation. Alternate splicing results in multiple transcript variants. Pseudgenes of this gene are found on chromosomes 7, 8 and 16. [provided by RefSeq, Apr 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCA8	NM_001256875.2	c.584+559G>A		intron_variant		ENST00000373055.6	NP_001243804.1
CDCA8	NM_018101.4	c.584+559G>A		intron_variant			NP_060571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDCA8	ENST00000373055.6	c.584+559G>A		intron_variant		1	NM_001256875.2	ENSP00000362146.1
CDCA8	ENST00000327331.2	c.584+559G>A		intron_variant		1		ENSP00000316121.2

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35337 AN: 151790 Hom.: 4393 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.233 AC: 35339 AN: 151908 Hom.: 4386 Cov.: 31 AF XY: 0.232 AC XY: 17224 AN XY: 74220

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.244

Alfa AF: 0.264 Hom.: 7336

Bravo AF: 0.230

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.36
DANN	Benign	0.77

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: rs3790623; hg19: chr1-38169578;