rs4340737

Variant names:

• chr3-119903167-C-T
• rs4340737
• NM_001146156.2:c.813+2588G>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.813+2588G>A 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 152,064 control chromosomes in the GnomAD database, including 4,890 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 (4890 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 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.813+2588G>A		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.813+2588G>A		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.813+2588G>A		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.813+2588G>A		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.813+2588G>A		intron	N/A	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.813+2588G>A		intron	N/A	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36712 AN: 151946 Hom.: 4886 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.242 AC: 36758 AN: 152064 Hom.: 4890 Cov.: 32 AF XY: 0.245 AC XY: 18235 AN XY: 74324

African (AFR) AF: 0.311 AC: 12904 AN: 41450

American (AMR) AF: 0.203 AC: 3098 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3472

East Asian (EAS) AF: 0.484 AC: 2500 AN: 5160

South Asian (SAS) AF: 0.298 AC: 1434 AN: 4814

European-Finnish (FIN) AF: 0.266 AC: 2816 AN: 10574

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12626 AN: 68000

Other (OTH) AF: 0.226 AC: 477 AN: 2112

Alfa AF: 0.204 Hom.: 10624

Bravo AF: 0.240

Asia WGS AF: 0.367 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.63
DANN	Benign	0.56
PhyloP100		-0.59
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: rs4340737; hg19: chr3-119622014;