rs11919783

Positions:

• chr3-120027786-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.89-25547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 152,176 control chromosomes in the GnomAD database, including 689 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 (689 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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=-0.49).
• 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/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.89-25547C>T		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.89-25547C>T		intron_variant
GSK3B	NM_002093.4	c.89-25547C>T		intron_variant
GSK3B	XM_006713610.4	c.89-25547C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.89-25547C>T		intron_variant		1	NM_001146156.2	A1
	ENST00000678483.1	n.30+40389C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0854 AC: 12990 AN: 152058 Hom.: 689 Cov.: 32

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0901

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0392

Gnomad FIN AF: 0.0488

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: 0.0854 AC: 12990 AN: 152176 Hom.: 689 Cov.: 32 AF XY: 0.0824 AC XY: 6131 AN XY: 74416

Gnomad4 AFR AF: 0.0546

Gnomad4 AMR AF: 0.0899

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0386

Gnomad4 FIN AF: 0.0488

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.104

Alfa AF: 0.103 Hom.: 398

Bravo AF: 0.0874

Asia WGS AF: 0.0240 AC: 82 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.3
DANN	Benign	0.82

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: rs11919783; hg19: chr3-119746633;