rs11921360

Variant names:

• chr3-119893208-C-A
• rs11921360
• NM_001146156.2:c.813+12547G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-119893208-C-A
• chr3-119893208-C-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.813+12547G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 151,848 control chromosomes in the GnomAD database, including 42,103 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 0.73 (42103 hom., cov: 30)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982
• Publications: 7 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 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.813+12547G>T		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.813+12547G>T		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.813+12547G>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.813+12547G>T		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.813+12547G>T		intron	N/A	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.813+12547G>T		intron	N/A	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111073 AN: 151730 Hom.: 42035 Cov.: 30

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.732 AC: 111201 AN: 151848 Hom.: 42103 Cov.: 30 AF XY: 0.728 AC XY: 54045 AN XY: 74200

African (AFR) AF: 0.934 AC: 38709 AN: 41454

American (AMR) AF: 0.757 AC: 11537 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2263 AN: 3466

East Asian (EAS) AF: 0.640 AC: 3291 AN: 5146

South Asian (SAS) AF: 0.752 AC: 3612 AN: 4802

European-Finnish (FIN) AF: 0.583 AC: 6148 AN: 10542

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43399 AN: 67892

Other (OTH) AF: 0.731 AC: 1542 AN: 2108

Alfa AF: 0.696 Hom.: 4811

Bravo AF: 0.753

Asia WGS AF: 0.713 AC: 2477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.14
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: rs11921360; hg19: chr3-119612055;