rs11488590

chr1-1703669-G-A

Variant summary

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

The NM_024011.4(CDK11A):c.1912-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 148,568 control chromosomes in the GnomAD database, including 4,651 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 0.18 (4651 hom., cov: 30)
  • Exomes 𝑓: 0.075 (10159 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDK11A NM_024011.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

Genes affected

CDK11A (HGNC:1730): (cyclin dependent kinase 11A) This gene encodes a member of the serine/threonine protein kinase family. Members of this kinase family are known to be essential for eukaryotic cell cycle control. Due to a segmental duplication, this gene shares very high sequence identity with a neighboring gene. These two genes are frequently deleted or altered in neuroblastoma. The protein kinase encoded by this gene can be cleaved by caspases and may play a role in cell apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK11A	NM_024011.4	c.1912-45C>T		intron_variant		ENST00000404249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK11A	ENST00000404249.8	c.1912-45C>T		intron_variant		1	NM_024011.4	P1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26238 AN: 148456 Hom.: 4648 Cov.: 30

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.0774

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0835

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0935

Gnomad NFE AF: 0.0547

Gnomad OTH AF: 0.138

GnomAD3 exomes AF: 0.106 AC: 18894 AN: 178410 Hom.: 2154 AF XY: 0.105 AC XY: 10033 AN XY: 95834

Gnomad AFR exome AF: 0.427

Gnomad AMR exome AF: 0.0973

Gnomad ASJ exome AF: 0.0638

Gnomad EAS exome AF: 0.211

Gnomad SAS exome AF: 0.191

Gnomad FIN exome AF: 0.0829

Gnomad NFE exome AF: 0.0425

Gnomad OTH exome AF: 0.0761

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0749 AC: 105115 AN: 1403248 Hom.: 10159 Cov.: 38 AF XY: 0.0773 AC XY: 53684 AN XY: 694220

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.0969

Gnomad4 ASJ exome AF: 0.0783

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.0864

Gnomad4 NFE exome AF: 0.0477

Gnomad4 OTH exome AF: 0.0989

GnomAD4 genome AF: 0.177 AC: 26261 AN: 148568 Hom.: 4651 Cov.: 30 AF XY: 0.181 AC XY: 13096 AN XY: 72514

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0835

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.0982

Gnomad4 NFE AF: 0.0547

Gnomad4 OTH AF: 0.136

Alfa AF: 0.121 Hom.: 435

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.6
Dann	Benign	0.30

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: rs11488590; hg19: chr1-1635108; COSMIC: COSV52307748; COSMIC: COSV52307748;