chr3-119848254-C-A

Position:

• chr3-119848254-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146156.2(GSK3B):​c.1097-4901G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,978 control chromosomes in the GnomAD database, including 18,269 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 0.44 (18269 hom., cov: 31)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.1097-4901G>T		intron_variant		ENST00000264235.13	NP_001139628.1
GSK3B	NM_001354596.2	c.1096+15165G>T		intron_variant			NP_001341525.1
GSK3B	NM_002093.4	c.1136-4901G>T		intron_variant			NP_002084.2
GSK3B	XM_006713610.4	c.1135+15165G>T		intron_variant			XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.1097-4901G>T		intron_variant		1	NM_001146156.2	ENSP00000264235	A1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67355 AN: 151860 Hom.: 18274 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.443 AC: 67341 AN: 151978 Hom.: 18269 Cov.: 31 AF XY: 0.445 AC XY: 33078 AN XY: 74276

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.462

Alfa AF: 0.521 Hom.: 5027

Bravo AF: 0.418

Asia WGS AF: 0.421 AC: 1466 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.59

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: rs3107669; hg19: chr3-119567101; COSMIC: COSV51781927; COSMIC: COSV51781927;