1-1719406-G-A

Variant names:

• chr1-1719406-G-A
• rs1059831
• NM_024011.4:c.277C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024011.4(CDK11A):​c.277C>T​(p.Arg93Trp) variant causes a missense change. The variant allele was found at a frequency of 0.806 in 150,506 control chromosomes in the GnomAD database, including 51,386 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 0.81 (51386 hom., cov: 31)
  • Exomes 𝑓: 0.90 (567696 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDK11A NM_024011.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25
• Publications: 30 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002390951).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

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.277C>T	p.Arg93Trp	missense	Exon 4 of 20	NP_076916.2	Q9UQ88-2
	CDK11A	NM_001313896.2		c.277C>T	p.Arg93Trp	missense	Exon 4 of 20	NP_001300825.1	Q9UQ88-1
	CDK11A	NM_001313982.2		c.277C>T	p.Arg93Trp	missense	Exon 4 of 20	NP_001300911.1	Q5QPR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK11A	ENST00000404249.8	TSL:1 MANE Select	c.277C>T	p.Arg93Trp	missense	Exon 4 of 20	ENSP00000384442.3	Q9UQ88-2
	CDK11A	ENST00000378633.5	TSL:1	c.277C>T	p.Arg93Trp	missense	Exon 4 of 20	ENSP00000367900.1	Q9UQ88-1
	CDK11A	ENST00000357760.6	TSL:1	c.277C>T	p.Arg93Trp	missense	Exon 4 of 20	ENSP00000350403.2	Q5QPR3

Frequencies

GnomAD3 genomes AF: 0.806 AC: 121187 AN: 150394 Hom.: 51348 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.897

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.844

GnomAD2 exomes AF: 0.480 AC: 104733 AN: 218330 AF XY: 0.480

Gnomad AFR exome AF: 0.373

Gnomad AMR exome AF: 0.488

Gnomad ASJ exome AF: 0.494

Gnomad EAS exome AF: 0.459

Gnomad FIN exome AF: 0.495

Gnomad NFE exome AF: 0.496

Gnomad OTH exome AF: 0.490

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.905 AC: 1240435 AN: 1371344 Hom.: 567696 Cov.: 31 AF XY: 0.901 AC XY: 613585 AN XY: 680898

African (AFR) AF: 0.523 AC: 15553 AN: 29722

American (AMR) AF: 0.859 AC: 24106 AN: 28066

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 20797 AN: 23420

East Asian (EAS) AF: 0.817 AC: 28913 AN: 35408

South Asian (SAS) AF: 0.735 AC: 53646 AN: 72990

European-Finnish (FIN) AF: 0.902 AC: 47002 AN: 52132

Middle Eastern (MID) AF: 0.857 AC: 4686 AN: 5470

European-Non Finnish (NFE) AF: 0.933 AC: 996003 AN: 1067652

Other (OTH) AF: 0.880 AC: 49729 AN: 56484

GnomAD4 genome AF: 0.806 AC: 121278 AN: 150506 Hom.: 51386 Cov.: 31 AF XY: 0.802 AC XY: 58930 AN XY: 73498

African (AFR) AF: 0.549 AC: 22477 AN: 40922

American (AMR) AF: 0.887 AC: 13306 AN: 15006

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3099 AN: 3448

East Asian (EAS) AF: 0.781 AC: 4001 AN: 5122

South Asian (SAS) AF: 0.738 AC: 3499 AN: 4738

European-Finnish (FIN) AF: 0.894 AC: 9381 AN: 10498

Middle Eastern (MID) AF: 0.899 AC: 259 AN: 288

European-Non Finnish (NFE) AF: 0.929 AC: 62720 AN: 67528

Other (OTH) AF: 0.846 AC: 1747 AN: 2066

Alfa AF: 0.529 Hom.: 1068

Bravo AF: 0.798

ESP6500AA AF: 0.366 AC: 1388

ESP6500EA AF: 0.488 AC: 4017

ExAC AF: 0.478 AC: 57737

Asia WGS AF: 0.761 AC: 2628 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.26
Sift	Benign	0.094	T
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.45
MPC		0.78
ClinPred		0.055	T
GERP RS		5.3
Varity_R		0.19
gMVP		0.040
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1059831; hg19: chr1-1650845; COSMIC: COSV62266388; COSMIC: COSV62266388;