chr3-119905634-C-T

Position:

• chr3-119905634-C-T

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.813+121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 675,924 control chromosomes in the GnomAD database, including 275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (183 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (92 hom.)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.147

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=-0.95).
• BP6: Variant 3-119905634-C-T is Benign according to our data. Variant chr3-119905634-C-T is described in ClinVar as [Benign]. Clinvar id is 1251553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.813+121G>A		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.813+121G>A		intron_variant
GSK3B	NM_002093.4	c.813+121G>A		intron_variant
GSK3B	XM_006713610.4	c.813+121G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.813+121G>A		intron_variant		1	NM_001146156.2	A1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4151 AN: 152018 Hom.: 180 Cov.: 32

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00963

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000942

Gnomad OTH AF: 0.0187

GnomAD4 exome AF: 0.00654 AC: 3426 AN: 523788 Hom.: 92 AF XY: 0.00580 AC XY: 1630 AN XY: 281008

Gnomad4 AFR exome AF: 0.0913

Gnomad4 AMR exome AF: 0.00644

Gnomad4 ASJ exome AF: 0.000127

Gnomad4 EAS exome AF: 0.0287

Gnomad4 SAS exome AF: 0.00560

Gnomad4 FIN exome AF: 0.000129

Gnomad4 NFE exome AF: 0.000796

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome AF: 0.0274 AC: 4170 AN: 152136 Hom.: 183 Cov.: 32 AF XY: 0.0267 AC XY: 1988 AN XY: 74388

Gnomad4 AFR AF: 0.0919

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00965

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000942

Gnomad4 OTH AF: 0.0195

Alfa AF: 0.000918 Hom.: 1

Bravo AF: 0.0318

Asia WGS AF: 0.0210 AC: 72 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

Jun 15, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.54
DANN	Benign	0.75

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: rs72548703; hg19: chr3-119624481;