rs1154597

chr3-120017986-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146156.2(GSK3B):c.89-15747T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,230 control chromosomes in the GnomAD database, including 947 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 0.10 (947 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.89-15747T>C		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.89-15747T>C		intron_variant
GSK3B	NM_002093.4	c.89-15747T>C		intron_variant
GSK3B	XM_006713610.4	c.89-15747T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.89-15747T>C		intron_variant		1	NM_001146156.2	A1
	ENST00000678483.1	n.31-48913T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15935 AN: 152112 Hom.: 947 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0713

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.0858

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0594

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.105 AC: 15947 AN: 152230 Hom.: 947 Cov.: 32 AF XY: 0.105 AC XY: 7849 AN XY: 74442

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0713

Gnomad4 ASJ AF: 0.0688

Gnomad4 EAS AF: 0.0853

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0594

Gnomad4 NFE AF: 0.0820

Gnomad4 OTH AF: 0.108

Alfa AF: 0.103 Hom.: 147

Bravo AF: 0.105

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.5
Dann	Benign	0.70

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: rs1154597; hg19: chr3-119736833;