rs7624540

Variant names:

• chr3-119890100-C-A
• rs7624540
• NM_001146156.2:c.814-13592G>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.814-13592G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,890 control chromosomes in the GnomAD database, including 3,938 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 0.22 (3938 hom., cov: 31)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.814-13592G>T		intron_variant	Intron 7 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.814-13592G>T		intron_variant	Intron 7 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.814-13592G>T		intron_variant	Intron 7 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.814-13592G>T		intron_variant	Intron 7 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.814-13592G>T		intron_variant	Intron 7 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33433 AN: 151772 Hom.: 3936 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.220 AC: 33457 AN: 151890 Hom.: 3938 Cov.: 31 AF XY: 0.216 AC XY: 16059 AN XY: 74242

African (AFR) AF: 0.305 AC: 12608 AN: 41388

American (AMR) AF: 0.183 AC: 2787 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3472

East Asian (EAS) AF: 0.0874 AC: 450 AN: 5150

South Asian (SAS) AF: 0.196 AC: 942 AN: 4812

European-Finnish (FIN) AF: 0.114 AC: 1202 AN: 10568

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13993 AN: 67940

Other (OTH) AF: 0.236 AC: 498 AN: 2108

Alfa AF: 0.219 Hom.: 601

Bravo AF: 0.225

Asia WGS AF: 0.165 AC: 573 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.3
DANN	Benign	0.80
PhyloP100		-0.096
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: rs7624540; hg19: chr3-119608947;