chr19-1218524-G-T

Position:

• chr19-1218524-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.374+24G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,604,610 control chromosomes in the GnomAD database, including 19,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (4150 hom., cov: 33)
  • Exomes 𝑓: 0.13 (15434 hom.)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:11
• Conservation: PhyloP100: -2.61

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-1218524-G-T is Benign according to our data. Variant chr19-1218524-G-T is described in ClinVar as [Benign]. Clinvar id is 256204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-1218524-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.374+24G>T		intron_variant		ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.374+24G>T		intron_variant			NP_001394184.1
STK11	NR_176325.1	n.1641+24G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.374+24G>T		intron_variant		1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.374+24G>T		intron_variant				ENSP00000498804.1
STK11	ENST00000585748.3	c.2+24G>T		intron_variant		3		ENSP00000477641.2
STK11	ENST00000593219.5	n.*199+24G>T		intron_variant		3		ENSP00000466610.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30021 AN: 152132 Hom.: 4129 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.180

GnomAD3 exomes AF: 0.162 AC: 40165 AN: 247810 Hom.: 4617 AF XY: 0.154 AC XY: 20706 AN XY: 134864

Gnomad AFR exome AF: 0.376

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.0973

Gnomad EAS exome AF: 0.418

Gnomad SAS exome AF: 0.141

Gnomad FIN exome AF: 0.0759

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.128 AC: 185245 AN: 1452360 Hom.: 15434 Cov.: 28 AF XY: 0.126 AC XY: 91159 AN XY: 722988

Gnomad4 AFR exome AF: 0.369

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.0962

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.0761

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.198 AC: 30107 AN: 152250 Hom.: 4150 Cov.: 33 AF XY: 0.198 AC XY: 14736 AN XY: 74444

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.188

Alfa AF: 0.115 Hom.: 1011

Bravo AF: 0.215

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 17, 2020	- -

Peutz-Jeghers syndrome Benign:2

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

Squamous cell lung carcinoma Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing;in vivo

Faculté Pluridciplinaire Nador, Université Mohamed Premier

May 05, 2020

- -

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	-0.91
CADD	Benign	0.0040
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs2075604; hg19: chr19-1218523; COSMIC: COSV58819874; COSMIC: COSV58819874;