chr19-1189483-T-G

Variant names:

• chr19-1189483-T-G
• rs9304882
• ENST00000585748.3:c.-259T>G

Variant summary

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

The ENST00000585748.3(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 ENST00000585748.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 15 publications found

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]

STK11 Gene-Disease associations (from GenCC):

• familial pancreatic carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Peutz-Jeghers syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Genomics England PanelApp, G2P
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000585748.3. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000585748.3	TSL:3	c.-259T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 12	ENSP00000477641.2
	STK11	ENST00000585748.3	TSL:3	c.-259T>G		5_prime_UTR	Exon 3 of 12	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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.700 AC: 7 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.243 AC: 18 AN: 74

Other (OTH) AF: 0.333 AC: 2 AN: 6

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

African (AFR) AF: 0.291 AC: 12070 AN: 41492

American (AMR) AF: 0.158 AC: 2408 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 793 AN: 3472

East Asian (EAS) AF: 0.0332 AC: 172 AN: 5184

South Asian (SAS) AF: 0.187 AC: 902 AN: 4830

European-Finnish (FIN) AF: 0.262 AC: 2780 AN: 10614

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18786 AN: 67994

Other (OTH) AF: 0.231 AC: 487 AN: 2112

Alfa AF: 0.262 Hom.: 17834

Bravo AF: 0.245

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		-0.64

Splicing

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

Other links and lift over

dbSNP: rs9304882; hg19: chr19-1189482;