3-120014863-T-C

Variant names:

• chr3-120014863-T-C
• rs4688054
• NM_001146156.2:c.89-12624A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146156.2(GSK3B):​c.89-12624A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,978 control chromosomes in the GnomAD database, including 4,909 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 0.24 (4909 hom., cov: 31)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics

ENSG00000288662 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146156.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	NM_001146156.2	MANE Select	c.89-12624A>G		intron	N/A	NP_001139628.1	Q6FI27
	GSK3B	NM_002093.4		c.89-12624A>G		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.89-12624A>G		intron	N/A	NP_001341525.1	A0A3B3ITW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.89-12624A>G		intron	N/A	ENSP00000264235.9	P49841-1
	GSK3B	ENST00000316626.6	TSL:1	c.89-12624A>G		intron	N/A	ENSP00000324806.5	P49841-2
	GSK3B	ENST00000678439.1		c.89-12624A>G		intron	N/A	ENSP00000503868.1	A0A7I2YQK0

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36786 AN: 151860 Hom.: 4906 Cov.: 31

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.242 AC: 36832 AN: 151978 Hom.: 4909 Cov.: 31 AF XY: 0.246 AC XY: 18265 AN XY: 74298

African (AFR) AF: 0.314 AC: 13008 AN: 41420

American (AMR) AF: 0.201 AC: 3075 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 732 AN: 3470

East Asian (EAS) AF: 0.482 AC: 2494 AN: 5170

South Asian (SAS) AF: 0.297 AC: 1432 AN: 4824

European-Finnish (FIN) AF: 0.268 AC: 2828 AN: 10548

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12627 AN: 67954

Other (OTH) AF: 0.228 AC: 480 AN: 2108

Alfa AF: 0.206 Hom.: 1810

Bravo AF: 0.240

Asia WGS AF: 0.365 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.55
DANN	Benign	0.79
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4688054; hg19: chr3-119733710;