rs1719888

Positions:

• chr3-119860033-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.1096+3386G>A		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.1096+3386G>A		intron_variant
GSK3B	NM_002093.4	c.1135+3386G>A		intron_variant
GSK3B	XM_006713610.4	c.1135+3386G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.1096+3386G>A		intron_variant		1	NM_001146156.2	A1

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

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.931

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.940

Gnomad4 NFE AF: 0.918

Gnomad4 OTH AF: 0.901

Alfa AF: 0.916 Hom.: 53512

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1719888; hg19: chr3-119578880;