1-1707458-A-G

Variant names:

• chr1-1707458-A-G
• rs1059828
• NM_024011.4:c.1196T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024011.4(CDK11A):​c.1196T>C​(p.Leu399Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00283 in 148,598 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0028 (2 hom., cov: 28)
  • Exomes 𝑓: 0.00019 (22 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDK11A NM_024011.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.41
• Publications: 9 publications found

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]

ENSG00000268575 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005014986).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024011.4. 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
	CDK11A	NM_024011.4	MANE Select	c.1196T>C	p.Leu399Ser	missense	Exon 11 of 20	NP_076916.2
	CDK11A	NM_001313896.2		c.1205T>C	p.Leu402Ser	missense	Exon 11 of 20	NP_001300825.1
	CDK11A	NM_001313982.2		c.1193T>C	p.Leu398Ser	missense	Exon 11 of 20	NP_001300911.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK11A	ENST00000404249.8	TSL:1 MANE Select	c.1196T>C	p.Leu399Ser	missense	Exon 11 of 20	ENSP00000384442.3
	CDK11A	ENST00000378633.5	TSL:1	c.1205T>C	p.Leu402Ser	missense	Exon 11 of 20	ENSP00000367900.1
	CDK11A	ENST00000357760.6	TSL:1	c.1193T>C	p.Leu398Ser	missense	Exon 11 of 20	ENSP00000350403.2

Frequencies

GnomAD3 genomes AF: 0.00283 AC: 420 AN: 148488 Hom.: 2 Cov.: 28

Gnomad AFR AF: 0.00979

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000869

Gnomad ASJ AF: 0.000583

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000193

Gnomad OTH AF: 0.00299

GnomAD2 exomes AF: 0.00348 AC: 849 AN: 244268 AF XY: 0.00328

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.00160

Gnomad ASJ exome AF: 0.000801

Gnomad EAS exome AF: 0.00426

Gnomad FIN exome AF: 0.000233

Gnomad NFE exome AF: 0.00152

Gnomad OTH exome AF: 0.00320

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000192 AC: 279 AN: 1455460 Hom.: 22 Cov.: 31 AF XY: 0.000171 AC XY: 124 AN XY: 723980

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00601 AC: 198 AN: 32930

American (AMR) AF: 0.000382 AC: 17 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39590

South Asian (SAS) AF: 0.000187 AC: 16 AN: 85764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5702

European-Non Finnish (NFE) AF: 0.0000244 AC: 27 AN: 1107614

Other (OTH) AF: 0.000267 AC: 16 AN: 60000

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00283 AC: 421 AN: 148598 Hom.: 2 Cov.: 28 AF XY: 0.00266 AC XY: 193 AN XY: 72622

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00978 AC: 386 AN: 39460

American (AMR) AF: 0.000868 AC: 13 AN: 14982

Ashkenazi Jewish (ASJ) AF: 0.000583 AC: 2 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.000214 AC: 1 AN: 4674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000193 AC: 13 AN: 67186

Other (OTH) AF: 0.00296 AC: 6 AN: 2028

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00165 Hom.: 4

ExAC AF: 0.00913 AC: 1102

EpiCase AF: 0.00378

EpiControl AF: 0.00305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.18
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.0	N
PhyloP100		5.4
PROVEAN	Benign	2.4	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.33
MVP		0.12
MPC		0.27
ClinPred		0.0020	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.029
gMVP		0.22
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1059828; hg19: chr1-1638897; COSMIC: COSV62265934; COSMIC: COSV62265934;