3-119916215-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001146156.2(GSK3B):c.478-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,517,208 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (81 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (57 hom.)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.115

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-119916215-T-C is Benign according to our data. Variant chr3-119916215-T-C is described in ClinVar as [Benign]. Clinvar id is 1262531.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.478-41A>G		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.478-41A>G		intron_variant
GSK3B	NM_002093.4	c.478-41A>G		intron_variant
GSK3B	XM_006713610.4	c.478-41A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.478-41A>G		intron_variant		1	NM_001146156.2	A1

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2637 AN: 152158 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00603

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00428 AC: 1014 AN: 236980 Hom.: 27 AF XY: 0.00293 AC XY: 377 AN XY: 128844

Gnomad AFR exome AF: 0.0592

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000140

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000741

Gnomad OTH exome AF: 0.00158

GnomAD4 exome AF: 0.00161 AC: 2202 AN: 1364932 Hom.: 57 Cov.: 20 AF XY: 0.00130 AC XY: 886 AN XY: 683464

Gnomad4 AFR exome AF: 0.0571

Gnomad4 AMR exome AF: 0.00332

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000134

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000913

Gnomad4 OTH exome AF: 0.00289

GnomAD4 genome AF: 0.0173 AC: 2638 AN: 152276 Hom.: 81 Cov.: 32 AF XY: 0.0166 AC XY: 1234 AN XY: 74458

Gnomad4 AFR AF: 0.0606

Gnomad4 AMR AF: 0.00602

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00850 Hom.: 8

Bravo AF: 0.0190

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 25, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	10
Dann	Benign	0.64

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: rs9825770; hg19: chr3-119635062;