chr3-119876204-A-G

Position:

• chr3-119876204-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001146156.2(GSK3B):​c.909+209T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 152,252 control chromosomes in the GnomAD database, including 169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.036 (169 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.70

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=-0.42).
• BP6: Variant 3-119876204-A-G is Benign according to our data. Variant chr3-119876204-A-G is described in ClinVar as [Benign]. Clinvar id is 1180397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.909+209T>C		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.909+209T>C		intron_variant
GSK3B	NM_002093.4	c.909+209T>C		intron_variant
GSK3B	XM_006713610.4	c.909+209T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.909+209T>C		intron_variant		1	NM_001146156.2	A1

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5411 AN: 152134 Hom.: 169 Cov.: 32

Gnomad AFR AF: 0.00755

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0632

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0355 AC: 5410 AN: 152252 Hom.: 169 Cov.: 32 AF XY: 0.0372 AC XY: 2766 AN XY: 74448

Gnomad4 AFR AF: 0.00753

Gnomad4 AMR AF: 0.0304

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0743

Gnomad4 FIN AF: 0.0632

Gnomad4 NFE AF: 0.0414

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0392 Hom.: 26

Bravo AF: 0.0313

Asia WGS AF: 0.0850 AC: 295 AN: 3474

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.79

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: rs45567135; hg19: chr3-119595051;