Variant 3-120001977-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001146156.2(GSK3B):c.282+69T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,034,560 control chromosomes in the GnomAD database, including 1,387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 912 hom., cov: 32)

Exomes 𝑓: 0.0077 ( 475 hom. )

Consequence

GSK3B
NM_001146156.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.88

Variant links:

Genes affected

GSK3B (HGNC:4617): (glycogen synthase kinase 3 beta) The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease. [provided by RefSeq, Aug 2017]

GSK3B links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-120001977-A-G is Benign according to our data. Variant chr3-120001977-A-G is described in ClinVar as [Benign]. Clinvar id is 1263908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
GSK3B	NM_001146156.2 linkuse as main transcript	c.282+69T>C	intron_variant	ENST00000264235.13
GSK3B	NM_001354596.2 linkuse as main transcript	c.282+69T>C	intron_variant
GSK3B	NM_002093.4 linkuse as main transcript	c.282+69T>C	intron_variant
GSK3B	XM_006713610.4 linkuse as main transcript	c.282+69T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13 linkuse as main transcript	c.282+69T>C		intron_variant		1	NM_001146156.2	A1	P49841-1
	ENST00000678483.1 linkuse as main transcript	n.31-32904T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0617

AC:

9378

AN:

152112

Hom.:

907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0237

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.0420

GnomAD4 exome

AF:

0.00774

AC:

6827

AN:

882330

Hom.:

475

AF XY:

0.00689

AC XY:

3028

AN XY:

439534

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.0146

Gnomad4 ASJ exome

AF:

0.000863

Gnomad4 EAS exome

AF:

0.0321

Gnomad4 SAS exome

AF:

0.00466

Gnomad4 FIN exome

AF:

0.0000881

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.0165

GnomAD4 genome

AF:

0.0618

AC:

9408

AN:

152230

Hom.:

912

Cov.:

AF XY:

0.0595

AC XY:

4432

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.0237

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0110

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.0425

Alfa

AF:

0.0587

Hom.:

101

Bravo

AF:

0.0709

Asia WGS

AF:

0.0270

AC:

AN:

3478

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	clinical testing	GeneDx	Jun 15, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.032

DANN

Benign

0.29

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