rs1564282

Positions:

• chr4-858525-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GAK	NM_005255.4	c.3283+1081G>A		intron_variant		ENST00000314167.9	NP_005246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAK	ENST00000314167.9	c.3283+1081G>A		intron_variant		1	NM_005255.4	ENSP00000314499	P1

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

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0884

Alfa AF: 0.103 Hom.: 1161

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1564282; hg19: chr4-852313;