rs6769435

Variant names:

• chr3-119965560-A-C
• rs6769435
• NM_001146156.2:c.283-18209T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-119965560-A-C
• chr3-119965560-A-G

Variant summary

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

The NM_001146156.2(GSK3B):​c.283-18209T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,970 control chromosomes in the GnomAD database, including 7,681 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 (7681 hom., cov: 30)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	NM_001146156.2	MANE Select	c.283-18209T>G		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.283-18209T>G		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.283-18209T>G		intron	N/A	NP_001341525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.283-18209T>G		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.283-18209T>G		intron	N/A	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.283-18209T>G		intron	N/A	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42310 AN: 151852 Hom.: 7667 Cov.: 30

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.279 AC: 42370 AN: 151970 Hom.: 7681 Cov.: 30 AF XY: 0.273 AC XY: 20285 AN XY: 74296

African (AFR) AF: 0.523 AC: 21620 AN: 41340

American (AMR) AF: 0.203 AC: 3098 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 681 AN: 3468

East Asian (EAS) AF: 0.0964 AC: 499 AN: 5174

South Asian (SAS) AF: 0.199 AC: 962 AN: 4824

European-Finnish (FIN) AF: 0.109 AC: 1150 AN: 10594

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13492 AN: 67974

Other (OTH) AF: 0.276 AC: 583 AN: 2110

Alfa AF: 0.266 Hom.: 1032

Bravo AF: 0.294

Asia WGS AF: 0.191 AC: 664 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.56
PhyloP100		-1.0
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: rs6769435; hg19: chr3-119684407;