Genetic Variant GSK3B:c.*3511T>A (chr3-119823277-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001146156.2(GSK3B):c.*3511T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 215,980 control chromosomes in the GnomAD database, including 7,090 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4957 hom., cov: 32)

Exomes 𝑓: 0.24 ( 2133 hom. )

Consequence

GSK3B
NM_001146156.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64

Publications

13 publications found

Variant links:

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

GSK3B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GSK3B	NM_001146156.2	MANE Select	c.*3511T>A	3_prime_UTR	Exon 11 of 11	NP_001139628.1
GSK3B	NM_002093.4		c.*3511T>A	3_prime_UTR	Exon 12 of 12	NP_002084.2
GSK3B	NM_001354596.2		c.*3511T>A	3_prime_UTR	Exon 10 of 10	NP_001341525.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.*3511T>A	3_prime_UTR	Exon 11 of 11	ENSP00000264235.9
GSK3B	ENST00000316626.6	TSL:1	c.*3511T>A	3_prime_UTR	Exon 12 of 12	ENSP00000324806.5
GSK3B	ENST00000678439.1		c.*3511T>A	3_prime_UTR	Exon 12 of 12	ENSP00000503868.1

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36911

AN:

152010

Hom.:

4952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.316

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.228

GnomAD4 exome

AF:

0.239

AC:

15238

AN:

63852

Hom.:

2133

Cov.:

AF XY:

0.240

AC XY:

7088

AN XY:

29490

show subpopulations

African (AFR)

AF:

0.321

AC:

939

AN:

2928

American (AMR)

AF:

0.202

AC:

383

AN:

1896

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

891

AN:

4060

East Asian (EAS)

AF:

0.470

AC:

4387

AN:

9336

South Asian (SAS)

AF:

0.276

AC:

147

AN:

532

European-Finnish (FIN)

AF:

0.227

AC:

AN:

Middle Eastern (MID)

AF:

0.224

AC:

AN:

384

European-Non Finnish (NFE)

AF:

0.183

AC:

7197

AN:

39248

Other (OTH)

AF:

0.221

AC:

1198

AN:

5424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

540

1080

1620

2160

2700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.243

AC:

36961

AN:

152128

Hom.:

4957

Cov.:

AF XY:

0.247

AC XY:

18347

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.316

AC:

13115

AN:

41484

American (AMR)

AF:

0.204

AC:

3113

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

752

AN:

3472

East Asian (EAS)

AF:

0.483

AC:

2499

AN:

5174

South Asian (SAS)

AF:

0.294

AC:

1418

AN:

4820

European-Finnish (FIN)

AF:

0.267

AC:

2825

AN:

10582

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12610

AN:

67996

Other (OTH)

AF:

0.227

AC:

480

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1402

2804

4207

5609

7011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.227

Hom.:

522

Bravo

AF:

0.241

Asia WGS

AF:

0.362

AC:

1255

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.8

(source)

DANN

Benign

0.62

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over