NM_001146156.2:c.814-148T>C

Variant names:

• chr3-119876656-A-G
• rs1719895
• NM_001146156.2:c.814-148T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146156.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	NM_001146156.2	MANE Select	c.814-148T>C		intron	N/A	NP_001139628.1	Q6FI27
	GSK3B	NM_002093.4		c.814-148T>C		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.814-148T>C		intron	N/A	NP_001341525.1	A0A3B3ITW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.814-148T>C		intron	N/A	ENSP00000264235.9	P49841-1
	GSK3B	ENST00000316626.6	TSL:1	c.814-148T>C		intron	N/A	ENSP00000324806.5	P49841-2
	GSK3B	ENST00000678439.1		c.814-148T>C		intron	N/A	ENSP00000503868.1	A0A7I2YQK0

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

African (AFR) AF: 0.833 AC: 10265 AN: 12320

American (AMR) AF: 0.945 AC: 18067 AN: 19116

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 12710 AN: 13636

East Asian (EAS) AF: 0.937 AC: 29048 AN: 31008

South Asian (SAS) AF: 0.849 AC: 37068 AN: 43636

European-Finnish (FIN) AF: 0.940 AC: 30019 AN: 31942

Middle Eastern (MID) AF: 0.913 AC: 1776 AN: 1946

European-Non Finnish (NFE) AF: 0.917 AC: 248405 AN: 270888

Other (OTH) AF: 0.907 AC: 23598 AN: 26010

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

African (AFR) AF: 0.831 AC: 34515 AN: 41512

American (AMR) AF: 0.929 AC: 14177 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3256 AN: 3472

East Asian (EAS) AF: 0.914 AC: 4737 AN: 5182

South Asian (SAS) AF: 0.845 AC: 4081 AN: 4832

European-Finnish (FIN) AF: 0.940 AC: 9968 AN: 10600

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.918 AC: 62449 AN: 68006

Other (OTH) AF: 0.892 AC: 1886 AN: 2114

Alfa AF: 0.907 Hom.: 34727

Bravo AF: 0.894

Asia WGS AF: 0.863 AC: 3002 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.65
DANN	Benign	0.30
PhyloP100		-2.7
PromoterAI		0.0030	Neutral
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: rs1719895; hg19: chr3-119595503;