rs6770314

chr3-120023874-G-A

Variant summary

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

The NM_001146156.2(GSK3B):c.89-21635C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,084 control chromosomes in the GnomAD database, including 8,014 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 0.28 (8014 hom., cov: 31)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.89-21635C>T		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.89-21635C>T		intron_variant
GSK3B	NM_002093.4	c.89-21635C>T		intron_variant
GSK3B	XM_006713610.4	c.89-21635C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.89-21635C>T		intron_variant		1	NM_001146156.2	A1
	ENST00000678483.1	n.30+44301C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42941 AN: 151966 Hom.: 8003 Cov.: 31

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0976

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.283 AC: 43001 AN: 152084 Hom.: 8014 Cov.: 31 AF XY: 0.277 AC XY: 20584 AN XY: 74342

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0970

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.279

Alfa AF: 0.220 Hom.: 2004

Bravo AF: 0.298

Asia WGS AF: 0.192 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.2
Dann	Benign	0.43

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: rs6770314; hg19: chr3-119742721;