19-1222013-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000455.5(STK11):​c.920+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,565,116 control chromosomes in the GnomAD database, including 32,560 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2372 hom., cov: 34)
Exomes 𝑓: 0.20 ( 30188 hom. )

Consequence

STK11
NM_000455.5 splice_region, intron

Scores

2
Splicing: ADA: 0.0001400
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:17

Conservation

PhyloP100: 1.13
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 19-1222013-G-C is Benign according to our data. Variant chr19-1222013-G-C is described in ClinVar as [Benign]. Clinvar id is 93099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-1222013-G-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STK11NM_000455.5 linkc.920+7G>C splice_region_variant, intron_variant Intron 7 of 9 ENST00000326873.12 NP_000446.1 Q15831-1A0A0S2Z4D1
STK11NM_001407255.1 linkc.920+7G>C splice_region_variant, intron_variant Intron 7 of 8 NP_001394184.1
STK11NR_176325.1 linkn.2187+7G>C splice_region_variant, intron_variant Intron 8 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STK11ENST00000326873.12 linkc.920+7G>C splice_region_variant, intron_variant Intron 7 of 9 1 NM_000455.5 ENSP00000324856.6 Q15831-1
STK11ENST00000652231.1 linkc.920+7G>C splice_region_variant, intron_variant Intron 7 of 8 ENSP00000498804.1 Q15831-2
STK11ENST00000585748.3 linkc.548+7G>C splice_region_variant, intron_variant Intron 9 of 11 3 ENSP00000477641.2 A0A087WT72

Frequencies

GnomAD3 genomes
AF:
0.159
AC:
24169
AN:
152196
Hom.:
2374
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0575
Gnomad AMI
AF:
0.155
Gnomad AMR
AF:
0.153
Gnomad ASJ
AF:
0.162
Gnomad EAS
AF:
0.323
Gnomad SAS
AF:
0.189
Gnomad FIN
AF:
0.207
Gnomad MID
AF:
0.120
Gnomad NFE
AF:
0.200
Gnomad OTH
AF:
0.159
GnomAD3 exomes
AF:
0.186
AC:
31820
AN:
170686
Hom.:
3257
AF XY:
0.189
AC XY:
17329
AN XY:
91864
show subpopulations
Gnomad AFR exome
AF:
0.0549
Gnomad AMR exome
AF:
0.131
Gnomad ASJ exome
AF:
0.154
Gnomad EAS exome
AF:
0.329
Gnomad SAS exome
AF:
0.179
Gnomad FIN exome
AF:
0.215
Gnomad NFE exome
AF:
0.201
Gnomad OTH exome
AF:
0.170
GnomAD4 exome
AF:
0.203
AC:
286471
AN:
1412802
Hom.:
30188
Cov.:
33
AF XY:
0.202
AC XY:
141136
AN XY:
698508
show subpopulations
Gnomad4 AFR exome
AF:
0.0551
Gnomad4 AMR exome
AF:
0.132
Gnomad4 ASJ exome
AF:
0.156
Gnomad4 EAS exome
AF:
0.312
Gnomad4 SAS exome
AF:
0.179
Gnomad4 FIN exome
AF:
0.213
Gnomad4 NFE exome
AF:
0.210
Gnomad4 OTH exome
AF:
0.188
GnomAD4 genome
AF:
0.159
AC:
24170
AN:
152314
Hom.:
2372
Cov.:
34
AF XY:
0.161
AC XY:
12004
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0574
Gnomad4 AMR
AF:
0.152
Gnomad4 ASJ
AF:
0.162
Gnomad4 EAS
AF:
0.323
Gnomad4 SAS
AF:
0.190
Gnomad4 FIN
AF:
0.207
Gnomad4 NFE
AF:
0.200
Gnomad4 OTH
AF:
0.159
Alfa
AF:
0.145
Hom.:
658
Bravo
AF:
0.149
Asia WGS
AF:
0.225
AC:
780
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Uncertain:1Benign:17
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:8
-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Oct 13, 2015
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
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

- -

-
Clinical Genetics, Academic Medical Center
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

- -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Uncertain:1Benign:3
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Nov 14, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Peutz-Jeghers syndrome Benign:4
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 04, 2025
Labcorp Genetics (formerly Invitae), Labcorp
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

- -

Jul 07, 2023
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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. -

Mar 31, 2015
Color Diagnostics, LLC DBA Color Health
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
1.5
DANN
Benign
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00014
dbscSNV1_RF
Benign
0.0060
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2075607; hg19: chr19-1222012; COSMIC: COSV58821643; COSMIC: COSV58821643; API