rs1574154

Variant names:

• chr3-119908400-T-C
• rs1574154
• NM_001146156.2:c.716-2548A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-119908400-T-C
• chr3-119908400-T-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.716-2548A>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 152,060 control chromosomes in the GnomAD database, including 4,905 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 (4905 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 7 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.716-2548A>G		intron_variant	Intron 6 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.716-2548A>G		intron_variant	Intron 6 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.716-2548A>G		intron_variant	Intron 6 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.716-2548A>G		intron_variant	Intron 6 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.716-2548A>G		intron_variant	Intron 6 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36761 AN: 151942 Hom.: 4901 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.252

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: 36808 AN: 152060 Hom.: 4905 Cov.: 32 AF XY: 0.245 AC XY: 18237 AN XY: 74322

African (AFR) AF: 0.312 AC: 12958 AN: 41490

American (AMR) AF: 0.203 AC: 3096 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2508 AN: 5172

South Asian (SAS) AF: 0.297 AC: 1428 AN: 4810

European-Finnish (FIN) AF: 0.266 AC: 2808 AN: 10562

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12632 AN: 67964

Other (OTH) AF: 0.225 AC: 475 AN: 2112

Alfa AF: 0.211 Hom.: 716

Bravo AF: 0.240

Asia WGS AF: 0.368 AC: 1276 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.3
DANN	Benign	0.86
PhyloP100		1.5
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: rs1574154; hg19: chr3-119627247;