3-119852694-T-C

Variant names:

• chr3-119852694-T-C
• rs4624596
• NM_001146156.2:c.1097-9341A>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.1097-9341A>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 152,094 control chromosomes in the GnomAD database, including 4,921 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 (4921 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 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.1097-9341A>G		intron	N/A	NP_001139628.1	Q6FI27
	GSK3B	NM_002093.4		c.1136-9341A>G		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.1096+10725A>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.1097-9341A>G		intron	N/A	ENSP00000264235.9	P49841-1
	GSK3B	ENST00000316626.6	TSL:1	c.1136-9341A>G		intron	N/A	ENSP00000324806.5	P49841-2
	GSK3B	ENST00000678439.1		c.1097-9341A>G		intron	N/A	ENSP00000503868.1	A0A7I2YQK0

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36798 AN: 151976 Hom.: 4917 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.242 AC: 36844 AN: 152094 Hom.: 4921 Cov.: 32 AF XY: 0.246 AC XY: 18282 AN XY: 74360

African (AFR) AF: 0.312 AC: 12962 AN: 41482

American (AMR) AF: 0.203 AC: 3099 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2514 AN: 5180

South Asian (SAS) AF: 0.298 AC: 1436 AN: 4818

European-Finnish (FIN) AF: 0.267 AC: 2824 AN: 10566

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

European-Non Finnish (NFE) AF: 0.186 AC: 12630 AN: 67978

Other (OTH) AF: 0.225 AC: 475 AN: 2114

Alfa AF: 0.217 Hom.: 779

Bravo AF: 0.240

Asia WGS AF: 0.368 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.79
PhyloP100		-0.96
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: rs4624596; hg19: chr3-119571541;