Variant 4-849748-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005255.4(GAK):c.3861C>T(p.His1287=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,613,302 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 19 hom. )

Consequence

GAK
NM_005255.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0970

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 4-849748-G-A is Benign according to our data. Variant chr4-849748-G-A is described in ClinVar as [Benign]. Clinvar id is 787170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.097 with no splicing effect.

BS2

High AC in GnomAd4 at 445 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAK	NM_005255.4 linkuse as main transcript	c.3861C>T	p.His1287=	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.3861C>T	p.His1287=	synonymous_variant	28/28	1	NM_005255.4	P1	O14976-1

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

445

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00248

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00479

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00305

AC:

761

AN:

249136

Hom.:

AF XY:

0.00326

AC XY:

441

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.000757

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.00440

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00318

Gnomad FIN exome

AF:

0.000233

Gnomad NFE exome

AF:

0.00456

Gnomad OTH exome

AF:

0.00378

GnomAD4 exome

AF:

0.00422

AC:

6171

AN:

1461056

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

3083

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00231

Gnomad4 ASJ exome

AF:

0.00445

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00328

Gnomad4 FIN exome

AF:

0.000207

Gnomad4 NFE exome

AF:

0.00485

Gnomad4 OTH exome

AF:

0.00366

GnomAD4 genome

AF:

0.00292

AC:

445

AN:

152246

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00481

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00387

Hom.:

Bravo

AF:

0.00314

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00529

EpiControl

AF:

0.00546

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	Jun 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.23

DANN

Benign

0.59

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