chr1-1719406-G-A

Position:

• chr1-1719406-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.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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 (MetaRNN=0.002390951).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK11A	NM_024011.4	c.277C>T	p.Arg93Trp	missense_variant	4/20	ENST00000404249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK11A	ENST00000404249.8	c.277C>T	p.Arg93Trp	missense_variant	4/20	1	NM_024011.4	P1

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

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

Gnomad4 AFR exome AF: 0.523

Gnomad4 AMR exome AF: 0.859

Gnomad4 ASJ exome AF: 0.888

Gnomad4 EAS exome AF: 0.817

Gnomad4 SAS exome AF: 0.735

Gnomad4 FIN exome AF: 0.902

Gnomad4 NFE exome AF: 0.933

Gnomad4 OTH exome AF: 0.880

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

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.899

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.894

Gnomad4 NFE AF: 0.929

Gnomad4 OTH AF: 0.846

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 v4.3

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;D;D;D;D;D
MetaRNN	Benign	0.0024	T;T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	2.0	.;.;M;.;M;M;.
MutationTaster	Benign	0.96	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.6	N;N;N;N;N;D;D
REVEL	Benign	0.26
Sift	Benign	0.094	T;T;T;T;T;T;T
Sift4G	Uncertain	0.0080	D;D;D;D;D;D;.
Polyphen		1.0	D;D;D;D;D;D;.
Vest4		0.45
MPC		0.78
ClinPred		0.055	T
GERP RS		5.3
Varity_R		0.20
gMVP		0.040

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

Publications

LitVar

Other links and lift over

dbSNP: rs1059831; hg19: chr1-1650845; COSMIC: COSV62266388; COSMIC: COSV62266388;