chr3-119848254-C-A

Variant names:

• chr3-119848254-C-A
• rs3107669
• NM_001146156.2:c.1097-4901G>T

Variant summary

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

The NM_001146156.2(GSK3B):​c.1097-4901G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,978 control chromosomes in the GnomAD database, including 18,269 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 0.44 (18269 hom., cov: 31)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.1097-4901G>T		intron_variant	Intron 9 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.1136-4901G>T		intron_variant	Intron 10 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.1096+15165G>T		intron_variant	Intron 9 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.1135+15165G>T		intron_variant	Intron 10 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.1097-4901G>T		intron_variant	Intron 9 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67355 AN: 151860 Hom.: 18274 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.443 AC: 67341 AN: 151978 Hom.: 18269 Cov.: 31 AF XY: 0.445 AC XY: 33078 AN XY: 74276

African (AFR) AF: 0.114 AC: 4731 AN: 41476

American (AMR) AF: 0.473 AC: 7219 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2005 AN: 3466

East Asian (EAS) AF: 0.413 AC: 2132 AN: 5158

South Asian (SAS) AF: 0.497 AC: 2397 AN: 4820

European-Finnish (FIN) AF: 0.617 AC: 6497 AN: 10538

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40623 AN: 67930

Other (OTH) AF: 0.462 AC: 977 AN: 2114

Alfa AF: 0.512 Hom.: 5035

Bravo AF: 0.418

Asia WGS AF: 0.421 AC: 1466 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.59
PhyloP100		-0.11
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: rs3107669; hg19: chr3-119567101; COSMIC: COSV51781927; COSMIC: COSV51781927;