chr3-120049399-G-T

Variant names:

• chr3-120049399-G-T
• rs12630592
• NM_001146156.2:c.88+43948C>A

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+43948C>A 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 152,026 control chromosomes in the GnomAD database, including 24,309 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 0.53 (24309 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 23 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.88+43948C>A		intron_variant	Intron 1 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.88+43948C>A		intron_variant	Intron 1 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.88+43948C>A		intron_variant	Intron 1 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.88+43948C>A		intron_variant	Intron 1 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.88+43948C>A		intron_variant	Intron 1 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79760 AN: 151906 Hom.: 24253 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.525 AC: 79879 AN: 152026 Hom.: 24309 Cov.: 32 AF XY: 0.523 AC XY: 38886 AN XY: 74322

African (AFR) AF: 0.852 AC: 35377 AN: 41500

American (AMR) AF: 0.405 AC: 6193 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1413 AN: 3466

East Asian (EAS) AF: 0.579 AC: 2986 AN: 5160

South Asian (SAS) AF: 0.493 AC: 2376 AN: 4820

European-Finnish (FIN) AF: 0.377 AC: 3979 AN: 10552

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26055 AN: 67928

Other (OTH) AF: 0.505 AC: 1065 AN: 2110

Alfa AF: 0.435 Hom.: 29683

Bravo AF: 0.538

Asia WGS AF: 0.557 AC: 1933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.9
DANN	Benign	0.66
PhyloP100		-0.037
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: rs12630592; hg19: chr3-119768246;