rs2061846

chr4-858696-T-Cchr4-858696-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005255.4(GAK):c.3283+910A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,218 control chromosomes in the GnomAD database, including 2,414 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 0.17 (2414 hom., cov: 33)
• Consequence: GAK NM_005255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAK	NM_005255.4	c.3283+910A>G		intron_variant		ENST00000314167.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAK	ENST00000314167.9	c.3283+910A>G		intron_variant		1	NM_005255.4	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26227 AN: 152100 Hom.: 2419 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0766

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.172 AC: 26227 AN: 152218 Hom.: 2414 Cov.: 33 AF XY: 0.171 AC XY: 12695 AN XY: 74412

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.0766

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.181

Alfa AF: 0.153 Hom.: 1074

Bravo AF: 0.182

Asia WGS AF: 0.238 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.63
Dann	Benign	0.47

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: rs2061846; hg19: chr4-852484;