Variant 4-849718-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005255.4(GAK):c.3891C>T(p.Asp1297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,613,412 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 39 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 26 hom. )

Consequence

GAK
NM_005255.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.21

Variant links:

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]

GAK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 4-849718-G-A is Benign according to our data. Variant chr4-849718-G-A is described in ClinVar as [Benign]. Clinvar id is 778842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.21 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1734/152274) while in subpopulation AFR AF= 0.0352 (1465/41572). AF 95% confidence interval is 0.0337. There are 39 homozygotes in gnomad4. There are 803 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1734 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAK	NM_005255.4 linkuse as main transcript	c.3891C>T	p.Asp1297=	synonymous_variant	28/28	ENST00000314167.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAK	ENST00000314167.9 linkuse as main transcript	c.3891C>T	p.Asp1297=	synonymous_variant	28/28	1	NM_005255.4	P1	O14976-1

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1733

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0353

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00863

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00163

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00393

AC:

980

AN:

249490

Hom.:

AF XY:

0.00320

AC XY:

432

AN XY:

135178

show subpopulations

Gnomad AFR exome

AF:

0.0376

Gnomad AMR exome

AF:

0.00308

Gnomad ASJ exome

AF:

0.000898

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000984

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00220

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00262

AC:

3833

AN:

1461138

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1744

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.0370

Gnomad4 AMR exome

AF:

0.00307

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.000282

Gnomad4 NFE exome

AF:

0.00193

Gnomad4 OTH exome

AF:

0.00376

GnomAD4 genome

AF:

0.0114

AC:

1734

AN:

152274

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

803

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0352

Gnomad4 AMR

AF:

0.00862

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00163

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00585

Hom.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00218

EpiControl

AF:

0.00267

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.9

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over