chr3-120052424-G-C

Variant names:

• chr3-120052424-G-C
• rs16830689
• NM_001146156.2:c.88+40923C>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.88+40923C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,990 control chromosomes in the GnomAD database, including 8,063 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 0.28 (8063 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740
• Publications: 5 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

ENSG00000288662 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.88+40923C>G		intron_variant	Intron 1 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.88+40923C>G		intron_variant	Intron 1 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.88+40923C>G		intron_variant	Intron 1 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.88+40923C>G		intron_variant	Intron 1 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.88+40923C>G		intron_variant	Intron 1 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43046 AN: 151872 Hom.: 8050 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0976

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.284 AC: 43105 AN: 151990 Hom.: 8063 Cov.: 32 AF XY: 0.278 AC XY: 20625 AN XY: 74286

African (AFR) AF: 0.539 AC: 22341 AN: 41414

American (AMR) AF: 0.204 AC: 3113 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3466

East Asian (EAS) AF: 0.0970 AC: 503 AN: 5184

South Asian (SAS) AF: 0.200 AC: 963 AN: 4818

European-Finnish (FIN) AF: 0.109 AC: 1146 AN: 10554

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13483 AN: 67958

Other (OTH) AF: 0.279 AC: 588 AN: 2108

Alfa AF: 0.237 Hom.: 675

Bravo AF: 0.299

Asia WGS AF: 0.194 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.4
DANN	Benign	0.68
PhyloP100		-0.74
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: rs16830689; hg19: chr3-119771271;