rs56728675

Positions:

• chr3-119823343-G-A
• chr3-119823343-G-C
• chr3-119823343-G-T

Variant summary

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

The NM_001146156.2(GSK3B):​c.*3445C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 204,540 control chromosomes in the GnomAD database, including 6,742 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 0.24 (4929 hom., cov: 32)
  • Exomes 𝑓: 0.24 (1813 hom.)
• Consequence: GSK3B NM_001146156.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371

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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.*3445C>T		3_prime_UTR_variant	11/11	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.*3445C>T		3_prime_UTR_variant	12/12		NP_002084.2
GSK3B	NM_001354596.2	c.*3445C>T		3_prime_UTR_variant	10/10		NP_001341525.1
GSK3B	XM_006713610.4	c.*3445C>T		3_prime_UTR_variant	11/11		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235	c.*3445C>T		3_prime_UTR_variant	11/11	1	NM_001146156.2	ENSP00000264235.9
GSK3B	ENST00000316626	c.*3445C>T		3_prime_UTR_variant	12/12	1		ENSP00000324806.5
GSK3B	ENST00000678439	c.*3445C>T		3_prime_UTR_variant	12/12			ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36808 AN: 151942 Hom.: 4925 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.242 AC: 12697 AN: 52478 Hom.: 1813 Cov.: 0 AF XY: 0.242 AC XY: 5912 AN XY: 24414

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.242 AC: 36857 AN: 152062 Hom.: 4929 Cov.: 32 AF XY: 0.246 AC XY: 18299 AN XY: 74318

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.226

Alfa AF: 0.213 Hom.: 811

Bravo AF: 0.240

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.8
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56728675; hg19: chr3-119542190;