3-119921182-A-T

Variant names:

• chr3-119921182-A-T
• rs6438553
• NM_001146156.2:c.477+2191T>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.477+2191T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,108 control chromosomes in the GnomAD database, including 24,683 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 (24683 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• 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

ENSG00000297780 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146156.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	NM_001146156.2	MANE Select	c.477+2191T>A		intron	N/A	NP_001139628.1	Q6FI27
	GSK3B	NM_002093.4		c.477+2191T>A		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.477+2191T>A		intron	N/A	NP_001341525.1	A0A3B3ITW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.477+2191T>A		intron	N/A	ENSP00000264235.9	P49841-1
	GSK3B	ENST00000316626.6	TSL:1	c.477+2191T>A		intron	N/A	ENSP00000324806.5	P49841-2
	GSK3B	ENST00000678439.1		c.477+2191T>A		intron	N/A	ENSP00000503868.1	A0A7I2YQK0

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80752 AN: 151990 Hom.: 24639 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.532 AC: 80858 AN: 152108 Hom.: 24683 Cov.: 32 AF XY: 0.529 AC XY: 39307 AN XY: 74354

African (AFR) AF: 0.852 AC: 35387 AN: 41518

American (AMR) AF: 0.414 AC: 6321 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1447 AN: 3468

East Asian (EAS) AF: 0.583 AC: 3014 AN: 5174

South Asian (SAS) AF: 0.502 AC: 2420 AN: 4824

European-Finnish (FIN) AF: 0.380 AC: 4016 AN: 10570

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26733 AN: 67956

Other (OTH) AF: 0.512 AC: 1080 AN: 2110

Alfa AF: 0.482 Hom.: 2450

Bravo AF: 0.544

Asia WGS AF: 0.559 AC: 1940 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.046
DANN	Benign	0.16
PhyloP100		-2.0
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: rs6438553; hg19: chr3-119640029;