rs13320980

Variant names:

• chr3-119890313-T-C
• rs13320980
• NM_001146156.2:c.814-13805A>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.814-13805A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,912 control chromosomes in the GnomAD database, including 5,077 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 0.23 (5077 hom., cov: 31)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 8 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.814-13805A>G		intron_variant	Intron 7 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.814-13805A>G		intron_variant	Intron 7 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.814-13805A>G		intron_variant	Intron 7 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.814-13805A>G		intron_variant	Intron 7 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.814-13805A>G		intron_variant	Intron 7 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35216 AN: 151794 Hom.: 5077 Cov.: 31

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0582

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.232 AC: 35206 AN: 151912 Hom.: 5077 Cov.: 31 AF XY: 0.230 AC XY: 17118 AN XY: 74278

African (AFR) AF: 0.0609 AC: 2524 AN: 41460

American (AMR) AF: 0.271 AC: 4139 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 985 AN: 3460

East Asian (EAS) AF: 0.0582 AC: 300 AN: 5158

South Asian (SAS) AF: 0.297 AC: 1427 AN: 4810

European-Finnish (FIN) AF: 0.307 AC: 3238 AN: 10546

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21777 AN: 67912

Other (OTH) AF: 0.239 AC: 505 AN: 2114

Alfa AF: 0.294 Hom.: 3584

Bravo AF: 0.221

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.2
DANN	Benign	0.89
PhyloP100		-0.057
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: rs13320980; hg19: chr3-119609160;