chr19-1218524-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:12

Conservation

PhyloP100: -2.61

Publications

15 publications found

Variant links:

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

STK11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 256204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000455.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STK11	NM_000455.5	MANE Select	c.374+24G>T	intron	N/A	NP_000446.1
STK11	NM_001407255.1		c.374+24G>T	intron	N/A	NP_001394184.1
STK11	NR_176325.1		n.1641+24G>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STK11	ENST00000326873.12	TSL:1 MANE Select	c.374+24G>T	intron	N/A	ENSP00000324856.6
STK11	ENST00000652231.1		c.374+24G>T	intron	N/A	ENSP00000498804.1
STK11	ENST00000585748.3	TSL:3	c.2+24G>T	intron	N/A	ENSP00000477641.2

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

30021

AN:

152132

Hom.:

4129

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.162

AC:

40165

AN:

247810

AF XY:

0.154

show subpopulations

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 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.:

AF XY:

0.126

AC XY:

91159

AN XY:

722988

show subpopulations

African (AFR)

AF:

0.369

AC:

12291

AN:

33296

American (AMR)

AF:

0.213

AC:

9517

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.0962

AC:

2510

AN:

26082

East Asian (EAS)

AF:

0.420

AC:

16659

AN:

39656

South Asian (SAS)

AF:

0.139

AC:

11966

AN:

86064

European-Finnish (FIN)

AF:

0.0761

AC:

3964

AN:

52110

Middle Eastern (MID)

AF:

0.119

AC:

676

AN:

5702

European-Non Finnish (NFE)

AF:

0.107

AC:

118592

AN:

1104704

Other (OTH)

AF:

0.151

AC:

9070

AN:

60072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8142

16284

24426

32568

40710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4756

9512

14268

19024

23780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.198

AC:

30107

AN:

152250

Hom.:

4150

Cov.:

AF XY:

0.198

AC XY:

14736

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.370

AC:

15358

AN:

41538

American (AMR)

AF:

0.206

AC:

3157

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0954

AC:

331

AN:

3470

East Asian (EAS)

AF:

0.408

AC:

2115

AN:

5180

South Asian (SAS)

AF:

0.151

AC:

727

AN:

4826

European-Finnish (FIN)

AF:

0.0778

AC:

826

AN:

10614

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7103

AN:

68002

Other (OTH)

AF:

0.188

AC:

397

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1147

2294

3440

4587

5734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.138

Hom.:

4510

Bravo

AF:

0.215

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:3

Jan 17, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Hereditary cancer-predisposing syndrome

Benign:2

Nov 18, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

Jul 10, 2025

GeneKor MSA

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Peutz-Jeghers syndrome

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Squamous cell lung carcinoma

Uncertain:1

May 05, 2020

Faculté Pluridciplinaire Nador, Université Mohamed Premier

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing;in vivo

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0040

(source)

DANN

Benign

0.73

PhyloP100

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over