3-119972320-T-C

Variant names:

• chr3-119972320-T-C
• rs10934503
• NM_001146156.2:c.283-24969A>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.283-24969A>G 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 152,144 control chromosomes in the GnomAD database, including 4,892 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 (4892 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496
• 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

ENSG00000288662 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.283-24969A>G		intron_variant	Intron 2 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.283-24969A>G		intron_variant	Intron 2 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.283-24969A>G		intron_variant	Intron 2 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.283-24969A>G		intron_variant	Intron 2 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.283-24969A>G		intron_variant	Intron 2 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36713 AN: 152026 Hom.: 4888 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.242 AC: 36760 AN: 152144 Hom.: 4892 Cov.: 32 AF XY: 0.245 AC XY: 18219 AN XY: 74388

African (AFR) AF: 0.312 AC: 12937 AN: 41494

American (AMR) AF: 0.201 AC: 3078 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3472

East Asian (EAS) AF: 0.485 AC: 2512 AN: 5178

South Asian (SAS) AF: 0.297 AC: 1432 AN: 4822

European-Finnish (FIN) AF: 0.267 AC: 2823 AN: 10586

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12618 AN: 67982

Other (OTH) AF: 0.226 AC: 478 AN: 2114

Alfa AF: 0.225 Hom.: 676

Bravo AF: 0.239

Asia WGS AF: 0.367 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.3
DANN	Benign	0.71
PhyloP100		0.50
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: rs10934503; hg19: chr3-119691167;