rs9879992

Positions:

• chr3-119993874-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.282+8172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,118 control chromosomes in the GnomAD database, including 7,511 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 (7511 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.282+8172T>C		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.282+8172T>C		intron_variant
GSK3B	NM_002093.4	c.282+8172T>C		intron_variant
GSK3B	XM_006713610.4	c.282+8172T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.282+8172T>C		intron_variant		1	NM_001146156.2	A1
	ENST00000678483.1	n.31-24801T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41999 AN: 152000 Hom.: 7498 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.276 AC: 42053 AN: 152118 Hom.: 7511 Cov.: 32 AF XY: 0.271 AC XY: 20125 AN XY: 74362

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0968

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.273

Alfa AF: 0.255 Hom.: 923

Bravo AF: 0.291

Asia WGS AF: 0.192 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
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: rs9879992; hg19: chr3-119712721;