rs9304882

Positions:

• chr19-1189483-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000585748(STK11):​c.-259T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,270 control chromosomes in the GnomAD database, including 5,163 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 0.25 (5158 hom., cov: 32)
  • Exomes 𝑓: 0.29 (5 hom.)
• Consequence: STK11 ENST00000585748 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

Genes affected

STK11 (HGNC:11389): (serine/threonine kinase 11) The protein encoded by this gene is a serine/threonine kinase that regulates cell polarity and energy metabolism and functions as a tumor suppressor. Mutations in this gene have been associated with the autosomal dominant Peutz-Jeghers syndrome, as well as with skin, pancreatic, and testicular cancers. [provided by RefSeq, May 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.1189483T>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000585748	c.-259T>G		5_prime_UTR_premature_start_codon_gain_variant	3/12	3		ENSP00000477641.2
STK11	ENST00000585748	c.-259T>G		5_prime_UTR_variant	3/12	3		ENSP00000477641.2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38574 AN: 152054 Hom.: 5143 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.286 AC: 28 AN: 98 Hom.: 5 Cov.: 0 AF XY: 0.270 AC XY: 20 AN XY: 74

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.254 AC: 38636 AN: 152172 Hom.: 5158 Cov.: 32 AF XY: 0.247 AC XY: 18388 AN XY: 74404

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.0332

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.231

Alfa AF: 0.263 Hom.: 11132

Bravo AF: 0.245

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9304882; hg19: chr19-1189482;