chr3-119864829-T-C

Variant names:

• chr3-119864829-T-C
• rs1732170
• NM_001146156.2:c.910-1224A>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.910-1224A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,114 control chromosomes in the GnomAD database, including 19,860 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 0.47 (19860 hom., cov: 33)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.789
• Publications: 15 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.602 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.910-1224A>G		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.949-1224A>G		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.910-1224A>G		intron	N/A	NP_001341525.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.910-1224A>G		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.949-1224A>G		intron	N/A	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.910-1224A>G		intron	N/A	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71087 AN: 151994 Hom.: 19862 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.467 AC: 71087 AN: 152114 Hom.: 19860 Cov.: 33 AF XY: 0.470 AC XY: 34955 AN XY: 74350

African (AFR) AF: 0.144 AC: 5963 AN: 41522

American (AMR) AF: 0.586 AC: 8967 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2024 AN: 3472

East Asian (EAS) AF: 0.418 AC: 2165 AN: 5176

South Asian (SAS) AF: 0.502 AC: 2415 AN: 4814

European-Finnish (FIN) AF: 0.619 AC: 6529 AN: 10544

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41235 AN: 67978

Other (OTH) AF: 0.487 AC: 1028 AN: 2112

Alfa AF: 0.536 Hom.: 8619

Bravo AF: 0.455

Asia WGS AF: 0.437 AC: 1523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		0.79
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: rs1732170; hg19: chr3-119583676;