chr3-119922595-A-G

Position:

• chr3-119922595-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.477+778T>C		intron_variant		ENST00000264235.13	NP_001139628.1
GSK3B	NM_001354596.2	c.477+778T>C		intron_variant			NP_001341525.1
GSK3B	NM_002093.4	c.477+778T>C		intron_variant			NP_002084.2
GSK3B	XM_006713610.4	c.477+778T>C		intron_variant			XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.477+778T>C		intron_variant		1	NM_001146156.2	ENSP00000264235	A1

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

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.778

Alfa AF: 0.753 Hom.: 9526

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7431209; hg19: chr3-119641442;