19-1221935-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000455.5(STK11):c.863-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,551,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.82

Publications

0 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=-0.82).

BP6

Variant 19-1221935-C-T is Benign according to our data. Variant chr19-1221935-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 378678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000788 (12/152242) while in subpopulation AFR AF = 0.000193 (8/41466). AF 95% confidence interval is 0.0000956. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5 link	c.863-14C>T	intron_variant	Intron 6 of 9	ENST00000326873.12	NP_000446.1	Q15831-1A0A0S2Z4D1
STK11	NM_001407255.1 link	c.863-14C>T	intron_variant	Intron 6 of 8		NP_001394184.1
STK11	NR_176325.1 link	n.2130-14C>T	intron_variant	Intron 7 of 10

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
STK11	ENST00000326873.12 link	c.863-14C>T	intron_variant	Intron 6 of 9	1	NM_000455.5	ENSP00000324856.6	Q15831-1
STK11	ENST00000652231.1 link	c.863-14C>T	intron_variant	Intron 6 of 8			ENSP00000498804.1	Q15831-2
STK11	ENST00000585748.3 link	c.491-14C>T	intron_variant	Intron 8 of 11	3		ENSP00000477641.2	A0A087WT72
STK11	ENST00000593219.6 link	n.*688-14C>T	intron_variant	Intron 7 of 10	3		ENSP00000466610.1	K7EMR0

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000576

AC:

AN:

156172

AF XY:

0.0000722

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000898

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000328

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.0000279

AC:

AN:

1399672

Hom.:

Cov.:

AF XY:

0.0000391

AC XY:

AN XY:

690640

show subpopulations

African (AFR)

AF:

0.0000632

AC:

AN:

31652

American (AMR)

AF:

0.0000834

AC:

AN:

35966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25188

East Asian (EAS)

AF:

0.0000279

AC:

AN:

35874

South Asian (SAS)

AF:

0.0000504

AC:

AN:

79332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0000213

AC:

AN:

1079838

Other (OTH)

AF:

0.000103

AC:

AN:

58048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000537

Hom.:

Bravo

AF:

0.0000567

ClinVar

Significance: Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Peutz-Jeghers syndrome

Benign:4

Mar 27, 2025

Myriad Genetics, Inc.

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 01, 2023

All of Us Research Program, National Institutes of Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Nov 17, 2015

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Malignant tumor of breast

Benign:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

The STK11 c.863-14C>T variant was not identified in the literature, nor was it identified in the Cosmic, LOVD 3.0, Zhejiang University Database, or Insight Hereditary Tumors databases. The variant was identified in dbSNP (ID: rs756001994 as "With Likely benign, Uncertain significance allele") and in ClinVar (2x as likely benign by GeneDx and Color Genomics). The variant was identified in control databases in 12 of 181762 chromosomes at a frequency of 0.00007 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 4 of 16456 chromosomes (freq: 0.0002), Other in 1 of 4832 chromosomes (freq: 0.0002), Latino in 3 of 25082 chromosomes (freq: 0.0001), European in 2 of 73216 chromosomes (freq: 0.00003), East Asian in 1 of 12088 chromosomes (freq: 0.00008), and South Asian in 1 of 22908 chromosomes (freq: 0.00004), while the variant was not observed in the Ashkenazi Jewish or Finnish populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -

Hereditary cancer-predisposing syndrome

Benign:1

Apr 18, 2016

Color Diagnostics, LLC DBA Color Health

Significance:Likely 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

-0.82

CADD

Benign

0.076

(source)

DANN

Benign

0.55

PhyloP100

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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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19-1221935-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over