rs7431209

Variant names:

• chr3-119922595-A-G
• rs7431209
• NM_001146156.2:c.477+778T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-119922595-A-G
• chr3-119922595-A-T

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+778T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 150,468 control chromosomes in the GnomAD database, including 47,711 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 0.79 (47711 hom., cov: 29)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.477+778T>C		intron_variant	Intron 4 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.477+778T>C		intron_variant	Intron 4 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.477+778T>C		intron_variant	Intron 4 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.477+778T>C		intron_variant	Intron 4 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.477+778T>C		intron_variant	Intron 4 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.789 AC: 118628 AN: 150388 Hom.: 47661 Cov.: 29

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.721

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.789 AC: 118716 AN: 150468 Hom.: 47711 Cov.: 29 AF XY: 0.786 AC XY: 57682 AN XY: 73430

African (AFR) AF: 0.948 AC: 39121 AN: 41272

American (AMR) AF: 0.795 AC: 12005 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2445 AN: 3460

East Asian (EAS) AF: 0.642 AC: 3297 AN: 5132

South Asian (SAS) AF: 0.800 AC: 3846 AN: 4810

European-Finnish (FIN) AF: 0.693 AC: 6808 AN: 9828

Middle Eastern (MID) AF: 0.725 AC: 206 AN: 284

European-Non Finnish (NFE) AF: 0.722 AC: 48837 AN: 67612

Other (OTH) AF: 0.778 AC: 1610 AN: 2070

Alfa AF: 0.756 Hom.: 15880

Bravo AF: 0.802

Asia WGS AF: 0.735 AC: 2498 AN: 3404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.3
DANN	Benign	0.69
PhyloP100		0.32
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: rs7431209; hg19: chr3-119641442;