NM_001146156.2:c.909+4012T>A

Variant names:

• chr3-119872401-A-T
• rs4688043
• NM_001146156.2:c.909+4012T>A

Variant summary

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

The NM_001146156.2(GSK3B):​c.909+4012T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,178 control chromosomes in the GnomAD database, including 61,062 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 0.89 (61062 hom., cov: 31)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.916 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.909+4012T>A		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.909+4012T>A		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.909+4012T>A		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.909+4012T>A		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.909+4012T>A		intron	N/A	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.909+4012T>A		intron	N/A	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136093 AN: 152060 Hom.: 61016 Cov.: 31

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.896

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

GnomAD4 genome AF: 0.895 AC: 136198 AN: 152178 Hom.: 61062 Cov.: 31 AF XY: 0.894 AC XY: 66519 AN XY: 74386

African (AFR) AF: 0.832 AC: 34560 AN: 41518

American (AMR) AF: 0.929 AC: 14180 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3253 AN: 3468

East Asian (EAS) AF: 0.914 AC: 4731 AN: 5178

South Asian (SAS) AF: 0.844 AC: 4074 AN: 4826

European-Finnish (FIN) AF: 0.940 AC: 9964 AN: 10598

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.918 AC: 62448 AN: 68006

Other (OTH) AF: 0.893 AC: 1885 AN: 2110

Alfa AF: 0.898 Hom.: 7632

Bravo AF: 0.895

Asia WGS AF: 0.863 AC: 3003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.14
DANN	Benign	0.71
PhyloP100		-1.7
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: rs4688043; hg19: chr3-119591248;