3-119876656-A-G

Position:

• chr3-119876656-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001146156.2(GSK3B):​c.814-148T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 602,690 control chromosomes in the GnomAD database, including 248,832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (61034 hom., cov: 32)
  • Exomes 𝑓: 0.91 (187798 hom.)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.72

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 3-119876656-A-G is Benign according to our data. Variant chr3-119876656-A-G is described in ClinVar as [Benign]. Clinvar id is 1251228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.814-148T>C		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.814-148T>C		intron_variant
GSK3B	NM_002093.4	c.814-148T>C		intron_variant
GSK3B	XM_006713610.4	c.814-148T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.814-148T>C		intron_variant		1	NM_001146156.2	A1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136066 AN: 152070 Hom.: 60988 Cov.: 32

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.895

GnomAD4 exome AF: 0.912 AC: 410956 AN: 450502 Hom.: 187798 AF XY: 0.908 AC XY: 217415 AN XY: 239326

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.945

Gnomad4 ASJ exome AF: 0.932

Gnomad4 EAS exome AF: 0.937

Gnomad4 SAS exome AF: 0.849

Gnomad4 FIN exome AF: 0.940

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 0.907

GnomAD4 genome AF: 0.895 AC: 136171 AN: 152188 Hom.: 61034 Cov.: 32 AF XY: 0.894 AC XY: 66519 AN XY: 74406

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.940

Gnomad4 NFE AF: 0.918

Gnomad4 OTH AF: 0.892

Alfa AF: 0.907 Hom.: 31246

Bravo AF: 0.894

Asia WGS AF: 0.863 AC: 3002 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.65
DANN	Benign	0.30

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: rs1719895; hg19: chr3-119595503;