rs2873950

Variant names:

• chr3-119828215-A-C
• rs2873950
• NM_001146156.2:c.1196-1360T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-119828215-A-C
• chr3-119828215-A-G

Variant summary

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

The NM_002093.4(GSK3B):​c.1235-1360T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,070 control chromosomes in the GnomAD database, including 5,130 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 0.25 (5130 hom., cov: 32)
• Consequence: GSK3B NM_002093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 15 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002093.4. 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.1196-1360T>G		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.1235-1360T>G		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.1097-1360T>G		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.1196-1360T>G		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.1235-1360T>G		intron	N/A	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.1346-1360T>G		intron	N/A	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37401 AN: 151950 Hom.: 5124 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.246 AC: 37451 AN: 152070 Hom.: 5130 Cov.: 32 AF XY: 0.249 AC XY: 18537 AN XY: 74348

African (AFR) AF: 0.325 AC: 13477 AN: 41434

American (AMR) AF: 0.205 AC: 3130 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3466

East Asian (EAS) AF: 0.501 AC: 2592 AN: 5178

South Asian (SAS) AF: 0.296 AC: 1421 AN: 4806

European-Finnish (FIN) AF: 0.259 AC: 2739 AN: 10584

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12691 AN: 67996

Other (OTH) AF: 0.230 AC: 486 AN: 2114

Alfa AF: 0.199 Hom.: 3410

Bravo AF: 0.245

Asia WGS AF: 0.374 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.50
PhyloP100		-0.085
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: rs2873950; hg19: chr3-119547062;