chr3-119866843-T-A

Variant names:

• chr3-119866843-T-A
• rs7633279
• NM_001146156.2:c.910-3238A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001146156.2(GSK3B):​c.910-3238A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,894 control chromosomes in the GnomAD database, including 4,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (4889 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.571
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 3-119866843-T-A is Benign according to our data. Variant chr3-119866843-T-A is described in ClinVar as Benign. ClinVar VariationId is 1244745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 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.910-3238A>T		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.910-215A>T		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.910-3238A>T		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.910-3238A>T		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.910-215A>T		intron	N/A	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.910-3238A>T		intron	N/A	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36694 AN: 151776 Hom.: 4885 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.242 AC: 36741 AN: 151894 Hom.: 4889 Cov.: 32 AF XY: 0.245 AC XY: 18211 AN XY: 74214

African (AFR) AF: 0.312 AC: 12918 AN: 41416

American (AMR) AF: 0.203 AC: 3089 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3468

East Asian (EAS) AF: 0.486 AC: 2509 AN: 5166

South Asian (SAS) AF: 0.297 AC: 1430 AN: 4812

European-Finnish (FIN) AF: 0.267 AC: 2814 AN: 10538

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12607 AN: 67942

Other (OTH) AF: 0.224 AC: 472 AN: 2106

Alfa AF: 0.226 Hom.: 510

Bravo AF: 0.240

Asia WGS AF: 0.368 AC: 1276 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.47
DANN	Benign	0.27
PhyloP100		-0.57
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: rs7633279; hg19: chr3-119585690;