rs16830683

Variant names:

• chr3-120041321-C-T
• rs16830683
• NM_001146156.2:c.89-39082G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146156.2(GSK3B):​c.89-39082G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 302,540 control chromosomes in the GnomAD database, including 1,684 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 0.10 (946 hom., cov: 31)
  • Exomes 𝑓: 0.089 (738 hom.)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 6 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]

RFKP3 (HGNC:56487): (RFK pseudogene 3)

ENSG00000288662 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	NM_001146156.2	MANE Select	c.89-39082G>A		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.89-39082G>A		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.89-39082G>A		intron	N/A	NP_001341525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.89-39082G>A		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.89-39082G>A		intron	N/A	ENSP00000324806.5
	RFKP3	ENST00000491262.1	TSL:6	n.132C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15893 AN: 151762 Hom.: 946 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.0861

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0595

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0887 AC: 13361 AN: 150660 Hom.: 738 Cov.: 0 AF XY: 0.0935 AC XY: 8179 AN XY: 87512

African (AFR) AF: 0.165 AC: 583 AN: 3538

American (AMR) AF: 0.0392 AC: 576 AN: 14684

Ashkenazi Jewish (ASJ) AF: 0.0820 AC: 204 AN: 2488

East Asian (EAS) AF: 0.0802 AC: 494 AN: 6160

South Asian (SAS) AF: 0.154 AC: 3106 AN: 20112

European-Finnish (FIN) AF: 0.0658 AC: 958 AN: 14552

Middle Eastern (MID) AF: 0.0910 AC: 187 AN: 2054

European-Non Finnish (NFE) AF: 0.0826 AC: 6630 AN: 80224

Other (OTH) AF: 0.0910 AC: 623 AN: 6848

GnomAD4 genome AF: 0.105 AC: 15905 AN: 151880 Hom.: 946 Cov.: 31 AF XY: 0.105 AC XY: 7818 AN XY: 74242

African (AFR) AF: 0.166 AC: 6873 AN: 41366

American (AMR) AF: 0.0711 AC: 1084 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3468

East Asian (EAS) AF: 0.0855 AC: 440 AN: 5144

South Asian (SAS) AF: 0.154 AC: 743 AN: 4812

European-Finnish (FIN) AF: 0.0595 AC: 629 AN: 10566

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0819 AC: 5568 AN: 67962

Other (OTH) AF: 0.108 AC: 226 AN: 2102

Alfa AF: 0.102 Hom.: 135

Bravo AF: 0.105

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.9
DANN	Benign	0.40
PhyloP100		-0.23
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: rs16830683; hg19: chr3-119760168;