3-119912967-A-G

Variant names:

• chr3-119912967-A-G
• rs6438552
• NM_001146156.2:c.609-157T>C

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.609-157T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,972 control chromosomes in the GnomAD database, including 24,851 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (24851 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.66
• Publications: 69 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=-0.9).
• BP6: Variant 3-119912967-A-G is Benign according to our data. Variant chr3-119912967-A-G is described in ClinVar as Benign. ClinVar VariationId is 1283977.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.609-157T>C		intron_variant	Intron 5 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.609-157T>C		intron_variant	Intron 5 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.609-157T>C		intron_variant	Intron 5 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.609-157T>C		intron_variant	Intron 5 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.609-157T>C		intron_variant	Intron 5 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80875 AN: 151852 Hom.: 24790 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.533 AC: 80999 AN: 151972 Hom.: 24851 Cov.: 32 AF XY: 0.530 AC XY: 39377 AN XY: 74294

African (AFR) AF: 0.857 AC: 35553 AN: 41468

American (AMR) AF: 0.414 AC: 6313 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1446 AN: 3468

East Asian (EAS) AF: 0.585 AC: 3025 AN: 5170

South Asian (SAS) AF: 0.498 AC: 2401 AN: 4820

European-Finnish (FIN) AF: 0.381 AC: 4021 AN: 10564

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

European-Non Finnish (NFE) AF: 0.393 AC: 26716 AN: 67902

Other (OTH) AF: 0.513 AC: 1084 AN: 2112

Alfa AF: 0.445 Hom.: 43665

Bravo AF: 0.546

Asia WGS AF: 0.565 AC: 1959 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 16315267) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.25
DANN	Benign	0.50
PhyloP100		-1.7
PromoterAI		-0.0047	Neutral
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: rs6438552; hg19: chr3-119631814;