chr1-1713927-A-G

Variant names:

• chr1-1713927-A-G
• rs7528782
• NM_024011.4:c.489-1527T>C

Variant summary

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

The ENST00000404249.8(CDK11A):​c.489-1527T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.075 (898 hom., cov: 0)
• Consequence: CDK11A ENST00000404249.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.60
• Publications: 4 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 (BayesDel_noAF=-1.09).
• BS2: High Homozygotes in GnomAd4 at 898 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000404249.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK11A	NM_024011.4	MANE Select	c.489-1527T>C		intron	N/A	NP_076916.2
	CDK11A	NM_001313896.2		c.459-1527T>C		intron	N/A	NP_001300825.1
	CDK11A	NM_001313982.2		c.459-1500T>C		intron	N/A	NP_001300911.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK11A	ENST00000404249.8	TSL:1 MANE Select	c.489-1527T>C		intron	N/A	ENSP00000384442.3
	CDK11A	ENST00000378633.5	TSL:1	c.459-1527T>C		intron	N/A	ENSP00000367900.1
	CDK11A	ENST00000357760.6	TSL:1	c.459-1500T>C		intron	N/A	ENSP00000350403.2

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 2992 AN: 39728 Hom.: 894 Cov.: 0

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000547

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0195

Gnomad OTH AF: 0.0807

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0754 AC: 2999 AN: 39770 Hom.: 898 Cov.: 0 AF XY: 0.0702 AC XY: 1385 AN XY: 19734

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

African (AFR) AF: 0.109 AC: 2654 AN: 24346

American (AMR) AF: 0.0505 AC: 128 AN: 2534

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 15 AN: 410

East Asian (EAS) AF: 0.000549 AC: 1 AN: 1822

South Asian (SAS) AF: 0.00563 AC: 10 AN: 1776

European-Finnish (FIN) AF: 0.0158 AC: 23 AN: 1456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 48

European-Non Finnish (NFE) AF: 0.0195 AC: 132 AN: 6764

Other (OTH) AF: 0.0807 AC: 36 AN: 446

⚠️ 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: 0.740 Hom.: 12670

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.27
DANN	Benign	0.15
PhyloP100		-3.6
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: rs7528782; hg19: chr1-1645366; COSMIC: COSV62264739; COSMIC: COSV62264739;