1-1703669-G-A

Variant names:

• chr1-1703669-G-A
• rs11488590
• NM_024011.4:c.1912-45C>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.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
• Publications: 5 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 (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 rank	MANE	Protein	UniProt
CDK11A	NM_024011.4	c.1912-45C>T		intron_variant	Intron 17 of 19	ENST00000404249.8	NP_076916.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK11A	ENST00000404249.8	c.1912-45C>T		intron_variant	Intron 17 of 19	1	NM_024011.4	ENSP00000384442.3

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

GnomAD2 exomes AF: 0.106 AC: 18894 AN: 178410 AF XY: 0.105

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 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

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

African (AFR) AF: 0.444 AC: 13785 AN: 31036

American (AMR) AF: 0.0969 AC: 3647 AN: 37640

Ashkenazi Jewish (ASJ) AF: 0.0783 AC: 1918 AN: 24508

East Asian (EAS) AF: 0.170 AC: 6306 AN: 37010

South Asian (SAS) AF: 0.217 AC: 17132 AN: 78816

European-Finnish (FIN) AF: 0.0864 AC: 4323 AN: 50016

Middle Eastern (MID) AF: 0.122 AC: 685 AN: 5600

European-Non Finnish (NFE) AF: 0.0477 AC: 51583 AN: 1080620

Other (OTH) AF: 0.0989 AC: 5736 AN: 58002

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.435 AC: 17209 AN: 39598

American (AMR) AF: 0.104 AC: 1557 AN: 15020

Ashkenazi Jewish (ASJ) AF: 0.0835 AC: 284 AN: 3402

East Asian (EAS) AF: 0.211 AC: 1066 AN: 5060

South Asian (SAS) AF: 0.229 AC: 1070 AN: 4672

European-Finnish (FIN) AF: 0.0982 AC: 1024 AN: 10426

Middle Eastern (MID) AF: 0.0903 AC: 26 AN: 288

European-Non Finnish (NFE) AF: 0.0547 AC: 3676 AN: 67154

Other (OTH) AF: 0.136 AC: 280 AN: 2056

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
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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