NM_001146156.2:c.367-8819A>G

Variant names:

• chr3-119932302-T-C
• rs17204365
• NM_001146156.2:c.367-8819A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001146156.2(GSK3B):​c.367-8819A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0244 in 152,312 control chromosomes in the GnomAD database, including 64 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 0.024 (64 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.896
• Publications: 4 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

ENSG00000297780 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0244 (3714/152312) while in subpopulation AMR AF = 0.0369 (565/15302). AF 95% confidence interval is 0.0344. There are 64 homozygotes in GnomAd4. There are 1865 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3714 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.367-8819A>G		intron_variant	Intron 3 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.367-8819A>G		intron_variant	Intron 3 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.367-8819A>G		intron_variant	Intron 3 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.367-8819A>G		intron_variant	Intron 3 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.367-8819A>G		intron_variant	Intron 3 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3712 AN: 152194 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.00557

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.0296

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

GnomAD4 genome AF: 0.0244 AC: 3714 AN: 152312 Hom.: 64 Cov.: 32 AF XY: 0.0250 AC XY: 1865 AN XY: 74476

African (AFR) AF: 0.00556 AC: 231 AN: 41574

American (AMR) AF: 0.0369 AC: 565 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4828

European-Finnish (FIN) AF: 0.0419 AC: 445 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0321 AC: 2184 AN: 68022

Other (OTH) AF: 0.0298 AC: 63 AN: 2114

Alfa AF: 0.0289 Hom.: 105

Bravo AF: 0.0237

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism

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: rs17204365; hg19: chr3-119651149;