chr3-120058033-G-T

Variant names:

• chr3-120058033-G-T
• rs17204878
• NM_001146156.2:c.88+35314C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146156.2(GSK3B):​c.88+35314C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,736 control chromosomes in the GnomAD database, including 24,674 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 0.53 (24674 hom., cov: 31)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.720
• Publications: 5 publications found

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]

GSK3B Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics

ENSG00000288662 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.88+35314C>A		intron_variant	Intron 1 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.88+35314C>A		intron_variant	Intron 1 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.88+35314C>A		intron_variant	Intron 1 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.88+35314C>A		intron_variant	Intron 1 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.88+35314C>A		intron_variant	Intron 1 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80176 AN: 151620 Hom.: 24615 Cov.: 31

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.529 AC: 80295 AN: 151736 Hom.: 24674 Cov.: 31 AF XY: 0.527 AC XY: 39031 AN XY: 74096

African (AFR) AF: 0.862 AC: 35760 AN: 41468

American (AMR) AF: 0.408 AC: 6207 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3466

East Asian (EAS) AF: 0.579 AC: 2987 AN: 5158

South Asian (SAS) AF: 0.497 AC: 2390 AN: 4808

European-Finnish (FIN) AF: 0.377 AC: 3931 AN: 10418

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26095 AN: 67874

Other (OTH) AF: 0.509 AC: 1075 AN: 2112

Alfa AF: 0.430 Hom.: 19398

Bravo AF: 0.542

Asia WGS AF: 0.559 AC: 1939 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.0
DANN	Benign	0.19
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17204878; hg19: chr3-119776880;