rs34928889

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.375-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,548,922 control chromosomes in the GnomAD database, including 162,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16494 hom., cov: 34)

Exomes 𝑓: 0.45 ( 145691 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: -0.814

Publications

12 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), Orphanet, G2P, Genomics England PanelApp, ClinGen
familial ovarian cancer
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

STK11 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000455.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.86).

BP6

Variant 19-1219275-G-A is Benign according to our data. Variant chr19-1219275-G-A is described in ClinVar as Benign. ClinVar VariationId is 256205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 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	UniProt
STK11	NM_000455.5	MANE Select	c.375-49G>A	intron	N/A	NP_000446.1	A0A0S2Z4D1
STK11	NM_001407255.1		c.375-49G>A	intron	N/A	NP_001394184.1	Q15831-2
STK11	NR_176325.1		n.1642-49G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STK11	ENST00000326873.12	TSL:1 MANE Select	c.375-49G>A	intron	N/A	ENSP00000324856.6	Q15831-1
STK11	ENST00000652231.1		c.375-49G>A	intron	N/A	ENSP00000498804.1	Q15831-2
STK11	ENST00000585748.3	TSL:3	c.3-49G>A	intron	N/A	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69479

AN:

151980

Hom.:

16466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.846

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.446

GnomAD2 exomes

AF:

0.468

AC:

73682

AN:

157324

AF XY:

0.469

show subpopulations

Gnomad AFR exome

AF:

0.474

Gnomad AMR exome

AF:

0.411

Gnomad ASJ exome

AF:

0.410

Gnomad EAS exome

AF:

0.855

Gnomad FIN exome

AF:

0.467

Gnomad NFE exome

AF:

0.429

Gnomad OTH exome

AF:

0.452

GnomAD4 exome

AF:

0.451

AC:

629562

AN:

1396824

Hom.:

145691

Cov.:

AF XY:

0.451

AC XY:

310503

AN XY:

689184

show subpopulations

African (AFR)

AF:

0.468

AC:

14805

AN:

31668

American (AMR)

AF:

0.414

AC:

14870

AN:

35900

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

10417

AN:

25138

East Asian (EAS)

AF:

0.859

AC:

30842

AN:

35908

South Asian (SAS)

AF:

0.471

AC:

37329

AN:

79298

European-Finnish (FIN)

AF:

0.466

AC:

22470

AN:

48264

Middle Eastern (MID)

AF:

0.448

AC:

2548

AN:

5688

European-Non Finnish (NFE)

AF:

0.436

AC:

469487

AN:

1077012

Other (OTH)

AF:

0.462

AC:

26794

AN:

57948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

17724

35447

53171

70894

88618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14660

29320

43980

58640

73300

<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:

0.457

AC:

69563

AN:

152098

Hom.:

16494

Cov.:

AF XY:

0.463

AC XY:

34395

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.472

AC:

19580

AN:

41510

American (AMR)

AF:

0.434

AC:

6645

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1443

AN:

3472

East Asian (EAS)

AF:

0.846

AC:

4357

AN:

5150

South Asian (SAS)

AF:

0.483

AC:

2327

AN:

4820

European-Finnish (FIN)

AF:

0.456

AC:

4831

AN:

10584

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.426

AC:

28956

AN:

67950

Other (OTH)

AF:

0.452

AC:

956

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1919

3838

5757

7676

9595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.426

Hom.:

2992

Bravo

AF:

0.457

Asia WGS

AF:

0.661

AC:

2297

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary cancer-predisposing syndrome (2)

not provided (2)

not specified (1)

Peutz-Jeghers syndrome (1)

Squamous cell lung carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.1

(source)

DANN

Benign

0.63

PhyloP100

-0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Computational scores

Splicing

Publications

Other links and lift over