rs17810676

Variant names:

• chr3-120061702-T-C
• rs17810676
• NM_001146156.2:c.88+31645A>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+31645A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,102 control chromosomes in the GnomAD database, including 24,221 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 0.52 (24221 hom., cov: 33)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 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.88+31645A>G		intron	N/A	NP_001139628.1	Q6FI27
	GSK3B	NM_002093.4		c.88+31645A>G		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.88+31645A>G		intron	N/A	NP_001341525.1	A0A3B3ITW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.88+31645A>G		intron	N/A	ENSP00000264235.9	P49841-1
	GSK3B	ENST00000316626.6	TSL:1	c.88+31645A>G		intron	N/A	ENSP00000324806.5	P49841-2
	GSK3B	ENST00000678439.1		c.88+31645A>G		intron	N/A	ENSP00000503868.1	A0A7I2YQK0

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79744 AN: 151986 Hom.: 24178 Cov.: 33

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.525 AC: 79849 AN: 152102 Hom.: 24221 Cov.: 33 AF XY: 0.523 AC XY: 38861 AN XY: 74360

African (AFR) AF: 0.849 AC: 35232 AN: 41518

American (AMR) AF: 0.406 AC: 6193 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1414 AN: 3470

East Asian (EAS) AF: 0.581 AC: 3012 AN: 5184

South Asian (SAS) AF: 0.496 AC: 2396 AN: 4826

European-Finnish (FIN) AF: 0.376 AC: 3963 AN: 10548

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.385 AC: 26137 AN: 67970

Other (OTH) AF: 0.506 AC: 1069 AN: 2112

Alfa AF: 0.453 Hom.: 3653

Bravo AF: 0.537

Asia WGS AF: 0.556 AC: 1927 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.2
DANN	Benign	0.53
PhyloP100		0.33
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: rs17810676; hg19: chr3-119780549;