rs1719888

Variant names:

• chr3-119860033-C-T
• rs1719888
• NM_001146156.2:c.1096+3386G>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.1096+3386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,248 control chromosomes in the GnomAD database, including 62,026 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 0.90 (62026 hom., cov: 31)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.1096+3386G>A		intron_variant	Intron 9 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.1135+3386G>A		intron_variant	Intron 10 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.1096+3386G>A		intron_variant	Intron 9 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.1135+3386G>A		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.1096+3386G>A		intron_variant	Intron 9 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137252 AN: 152130 Hom.: 61973 Cov.: 31

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.902 AC: 137366 AN: 152248 Hom.: 62026 Cov.: 31 AF XY: 0.902 AC XY: 67140 AN XY: 74460

African (AFR) AF: 0.858 AC: 35606 AN: 41512

American (AMR) AF: 0.931 AC: 14234 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3256 AN: 3472

East Asian (EAS) AF: 0.913 AC: 4738 AN: 5192

South Asian (SAS) AF: 0.844 AC: 4075 AN: 4826

European-Finnish (FIN) AF: 0.940 AC: 9978 AN: 10612

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.918 AC: 62475 AN: 68028

Other (OTH) AF: 0.901 AC: 1901 AN: 2110

Alfa AF: 0.915 Hom.: 69949

Bravo AF: 0.903

Asia WGS AF: 0.867 AC: 3015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.42
DANN	Benign	0.29
PhyloP100		-0.67
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: rs1719888; hg19: chr3-119578880;