chr3-119843538-T-A

Position:

• chr3-119843538-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001146156.2(GSK3B):​c.1097-185A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 275,324 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (175 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (13 hom.)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.296

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-119843538-T-A is Benign according to our data. Variant chr3-119843538-T-A is described in ClinVar as [Benign]. Clinvar id is 1235258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.1097-185A>T		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.1097-16683A>T		intron_variant
GSK3B	NM_002093.4	c.1136-185A>T		intron_variant
GSK3B	XM_006713610.4	c.1136-16683A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.1097-185A>T		intron_variant		1	NM_001146156.2	A1

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3912 AN: 151026 Hom.: 172 Cov.: 31

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00832

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00987

Gnomad SAS AF: 0.00441

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000310

Gnomad OTH AF: 0.0164

GnomAD4 exome AF: 0.00383 AC: 476 AN: 124180 Hom.: 13 Cov.: 0 AF XY: 0.00376 AC XY: 259 AN XY: 68792

Gnomad4 AFR exome AF: 0.0819

Gnomad4 AMR exome AF: 0.00365

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0295

Gnomad4 SAS exome AF: 0.00430

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000195

Gnomad4 OTH exome AF: 0.00650

GnomAD4 genome AF: 0.0260 AC: 3927 AN: 151144 Hom.: 175 Cov.: 31 AF XY: 0.0253 AC XY: 1865 AN XY: 73838

Gnomad4 AFR AF: 0.0892

Gnomad4 AMR AF: 0.00831

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00989

Gnomad4 SAS AF: 0.00441

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000310

Gnomad4 OTH AF: 0.0162

Alfa AF: 0.0192 Hom.: 10

Bravo AF: 0.0296

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.68

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: rs113576547; hg19: chr3-119562385;