rs1381841

Variant names:

• chr3-119959955-A-G
• rs1381841
• NM_001146156.2:c.283-12604T>C

Variant summary

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

The NM_001146156.2(GSK3B):​c.283-12604T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 152,056 control chromosomes in the GnomAD database, including 690 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 0.085 (690 hom., cov: 28)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.918
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.283-12604T>C		intron_variant	Intron 2 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.283-12604T>C		intron_variant	Intron 2 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.283-12604T>C		intron_variant	Intron 2 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.283-12604T>C		intron_variant	Intron 2 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.283-12604T>C		intron_variant	Intron 2 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.0854 AC: 12977 AN: 151938 Hom.: 690 Cov.: 28

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0853 AC: 12977 AN: 152056 Hom.: 690 Cov.: 28 AF XY: 0.0823 AC XY: 6118 AN XY: 74334

African (AFR) AF: 0.0545 AC: 2259 AN: 41472

American (AMR) AF: 0.0898 AC: 1371 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 439 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0389 AC: 187 AN: 4810

European-Finnish (FIN) AF: 0.0485 AC: 513 AN: 10580

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7807 AN: 67966

Other (OTH) AF: 0.104 AC: 219 AN: 2106

Alfa AF: 0.0886 Hom.: 106

Bravo AF: 0.0875

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.2
DANN	Benign	0.67
PhyloP100		0.92
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: rs1381841; hg19: chr3-119678802;