rs1564282

Variant names:

• chr4-858525-C-T
• rs1564282
• NM_005255.4:c.3283+1081G>A

Variant summary

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

The NM_005255.4(GAK):​c.3283+1081G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 152,274 control chromosomes in the GnomAD database, including 774 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 0.083 (774 hom., cov: 33)
• Consequence: GAK NM_005255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• Publications: 61 publications found

Genes affected

GAK (HGNC:4113): (cyclin G associated kinase) In all eukaryotes, the cell cycle is governed by cyclin-dependent protein kinases (CDKs), whose activities are regulated by cyclins and CDK inhibitors in a diverse array of mechanisms that involve the control of phosphorylation and dephosphorylation of Ser, Thr or Tyr residues. Cyclins are molecules that possess a consensus domain called the 'cyclin box.' In mammalian cells, 9 cyclin species have been identified, and they are referred to as cyclins A through I. Cyclin G is a direct transcriptional target of the p53 tumor suppressor gene product and thus functions downstream of p53. GAK is an association partner of cyclin G and CDK5. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAK	NM_005255.4	c.3283+1081G>A		intron_variant	Intron 24 of 27	ENST00000314167.9	NP_005246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAK	ENST00000314167.9	c.3283+1081G>A		intron_variant	Intron 24 of 27	1	NM_005255.4	ENSP00000314499.4

Frequencies

GnomAD3 genomes AF: 0.0831 AC: 12650 AN: 152156 Hom.: 773 Cov.: 33

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0893

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

GnomAD4 genome AF: 0.0831 AC: 12651 AN: 152274 Hom.: 774 Cov.: 33 AF XY: 0.0872 AC XY: 6489 AN XY: 74454

African (AFR) AF: 0.0161 AC: 671 AN: 41566

American (AMR) AF: 0.0615 AC: 940 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 703 AN: 3472

East Asian (EAS) AF: 0.113 AC: 584 AN: 5186

South Asian (SAS) AF: 0.180 AC: 869 AN: 4826

European-Finnish (FIN) AF: 0.167 AC: 1766 AN: 10600

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6857 AN: 68008

Other (OTH) AF: 0.0884 AC: 187 AN: 2116

Alfa AF: 0.101 Hom.: 1510

Bravo AF: 0.0681

Asia WGS AF: 0.157 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs1564282; hg19: chr4-852313;