chr19-1220322-T-C

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.465-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,565,604 control chromosomes in the GnomAD database, including 53,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7549 hom., cov: 34)

Exomes 𝑓: 0.25 ( 46038 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: -1.93

Publications

17 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 19-1220322-T-C is Benign according to our data. Variant chr19-1220322-T-C is described in ClinVar as Benign. ClinVar VariationId is 873158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 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.465-51T>C	intron	N/A	NP_000446.1
STK11	NM_001407255.1		c.465-51T>C	intron	N/A	NP_001394184.1
STK11	NR_176325.1		n.1732-51T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STK11	ENST00000326873.12	TSL:1 MANE Select	c.465-51T>C	intron	N/A	ENSP00000324856.6
STK11	ENST00000652231.1		c.465-51T>C	intron	N/A	ENSP00000498804.1
STK11	ENST00000585748.3	TSL:3	c.93-51T>C	intron	N/A	ENSP00000477641.2

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45639

AN:

151988

Hom.:

7528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.293

GnomAD4 exome

AF:

0.247

AC:

348953

AN:

1413498

Hom.:

46038

Cov.:

AF XY:

0.247

AC XY:

172585

AN XY:

698524

show subpopulations

African (AFR)

AF:

0.422

AC:

13718

AN:

32514

American (AMR)

AF:

0.278

AC:

10579

AN:

38116

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6100

AN:

25142

East Asian (EAS)

AF:

0.544

AC:

20323

AN:

37376

South Asian (SAS)

AF:

0.290

AC:

23428

AN:

80730

European-Finnish (FIN)

AF:

0.250

AC:

12131

AN:

48538

Middle Eastern (MID)

AF:

0.307

AC:

1743

AN:

5682

European-Non Finnish (NFE)

AF:

0.226

AC:

245098

AN:

1086884

Other (OTH)

AF:

0.271

AC:

15833

AN:

58516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

14733

29466

44199

58932

73665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8832

17664

26496

35328

44160

<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:

0.301

AC:

45721

AN:

152106

Hom.:

7549

Cov.:

AF XY:

0.303

AC XY:

22498

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.424

AC:

17566

AN:

41478

American (AMR)

AF:

0.283

AC:

4326

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

813

AN:

3468

East Asian (EAS)

AF:

0.524

AC:

2703

AN:

5156

South Asian (SAS)

AF:

0.292

AC:

1408

AN:

4820

European-Finnish (FIN)

AF:

0.249

AC:

2635

AN:

10594

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.226

AC:

15347

AN:

67976

Other (OTH)

AF:

0.298

AC:

630

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1647

3295

4942

6590

8237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.256

Hom.:

679

Bravo

AF:

0.310

Asia WGS

AF:

0.433

AC:

1506

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

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

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

1.9

(source)

DANN

Benign

0.73

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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