chr3-120090758-G-A

Variant names:

• chr3-120090758-G-A
• rs334559
• NM_001146156.2:c.88+2589C>T

Variant summary

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

The NM_001146156.2(GSK3B):​c.88+2589C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,952 control chromosomes in the GnomAD database, including 7,459 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 0.28 (7459 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 6 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	NM_001146156.2	MANE Select	c.88+2589C>T		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.88+2589C>T		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.88+2589C>T		intron	N/A	NP_001341525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.88+2589C>T		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.88+2589C>T		intron	N/A	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.88+2589C>T		intron	N/A	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41881 AN: 151834 Hom.: 7447 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0977

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.276 AC: 41934 AN: 151952 Hom.: 7459 Cov.: 32 AF XY: 0.270 AC XY: 20072 AN XY: 74262

African (AFR) AF: 0.513 AC: 21239 AN: 41410

American (AMR) AF: 0.201 AC: 3061 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3466

East Asian (EAS) AF: 0.0971 AC: 503 AN: 5178

South Asian (SAS) AF: 0.199 AC: 958 AN: 4806

European-Finnish (FIN) AF: 0.109 AC: 1148 AN: 10558

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13481 AN: 67950

Other (OTH) AF: 0.272 AC: 576 AN: 2114

Alfa AF: 0.249 Hom.: 975

Bravo AF: 0.290

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.9
DANN	Benign	0.58
PhyloP100		0.33
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: rs334559; hg19: chr3-119809605;