19-1207239-G-T

Position:

• chr19-1207239-G-T

Variant summary

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

The NM_000455.5(STK11):​c.290+36G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,561,928 control chromosomes in the GnomAD database, including 53,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5916 hom., cov: 32)
  • Exomes 𝑓: 0.24 (47444 hom.)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.01

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-1207239-G-T is Benign according to our data. Variant chr19-1207239-G-T is described in ClinVar as [Benign]. Clinvar id is 256203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-1207239-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK11	NM_000455.5	c.290+36G>T		intron_variant		ENST00000326873.12
STK11	NM_001407255.1	c.290+36G>T		intron_variant
STK11	NR_176325.1	n.1426+36G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12	c.290+36G>T		intron_variant		1	NM_000455.5	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40211 AN: 151928 Hom.: 5898 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.262

GnomAD3 exomes AF: 0.292 AC: 50356 AN: 172400 Hom.: 8600 AF XY: 0.292 AC XY: 27119 AN XY: 92894

Gnomad AFR exome AF: 0.288

Gnomad AMR exome AF: 0.272

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.687

Gnomad SAS exome AF: 0.329

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.227

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.244 AC: 344372 AN: 1409882 Hom.: 47444 Cov.: 33 AF XY: 0.246 AC XY: 171435 AN XY: 696244

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.324

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.265 AC: 40278 AN: 152046 Hom.: 5916 Cov.: 32 AF XY: 0.273 AC XY: 20253 AN XY: 74286

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.267

Alfa AF: 0.234 Hom.: 4209

Bravo AF: 0.266

Asia WGS AF: 0.497 AC: 1730 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 02, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Peutz-Jeghers syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Hereditary cancer-predisposing syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2014

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs3764640; hg19: chr19-1207238;