chr19-1207239-G-T

Variant names:

Variant summary

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

The NM_000455.5(STK11):c.290+36G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,561,928 control chromosomes in the GnomAD database, including 53,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5916 hom., cov: 32)

Exomes 𝑓: 0.24 ( 47444 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.01

Publications

42 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: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), G2P, 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=-0.81).

BP6

Variant 19-1207239-G-T is Benign according to our data. Variant chr19-1207239-G-T is described in ClinVar as Benign. ClinVar VariationId is 256203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 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.290+36G>T	intron	N/A	NP_000446.1	A0A0S2Z4D1
STK11	NM_001407255.1		c.290+36G>T	intron	N/A	NP_001394184.1	Q15831-2
STK11	NR_176325.1		n.1426+36G>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STK11	ENST00000326873.12	TSL:1 MANE Select	c.290+36G>T	intron	N/A	ENSP00000324856.6	Q15831-1
STK11	ENST00000652231.1		c.290+36G>T	intron	N/A	ENSP00000498804.1	Q15831-2
STK11	ENST00000585748.3	TSL:3	c.-82-11178G>T	intron	N/A	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40211

AN:

151928

Hom.:

5898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.691

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.292

AC:

50356

AN:

172400

AF XY:

0.292

show subpopulations

Gnomad AFR exome

AF:

0.288

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.687

Gnomad FIN exome

AF:

0.289

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.244

AC:

344372

AN:

1409882

Hom.:

47444

Cov.:

AF XY:

0.246

AC XY:

171435

AN XY:

696244

show subpopulations

African (AFR)

AF:

0.284

AC:

9169

AN:

32322

American (AMR)

AF:

0.267

AC:

9871

AN:

36982

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

5751

AN:

24744

East Asian (EAS)

AF:

0.711

AC:

26330

AN:

37048

South Asian (SAS)

AF:

0.324

AC:

25951

AN:

80040

European-Finnish (FIN)

AF:

0.284

AC:

14110

AN:

49698

Middle Eastern (MID)

AF:

0.306

AC:

1729

AN:

5642

European-Non Finnish (NFE)

AF:

0.217

AC:

235874

AN:

1084956

Other (OTH)

AF:

0.267

AC:

15587

AN:

58450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

13797

27595

41392

55190

68987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8522

17044

25566

34088

42610

<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:

0.265

AC:

40278

AN:

152046

Hom.:

5916

Cov.:

AF XY:

0.273

AC XY:

20253

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.282

AC:

11684

AN:

41464

American (AMR)

AF:

0.255

AC:

3896

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

782

AN:

3470

East Asian (EAS)

AF:

0.691

AC:

3568

AN:

5166

South Asian (SAS)

AF:

0.335

AC:

1611

AN:

4802

European-Finnish (FIN)

AF:

0.284

AC:

3004

AN:

10588

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14897

AN:

67982

Other (OTH)

AF:

0.267

AC:

562

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1432

2864

4295

5727

7159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.241

Hom.:

8458

Bravo

AF:

0.266

Asia WGS

AF:

0.497

AC:

1730

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Hereditary cancer-predisposing syndrome (2)

Peutz-Jeghers syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.6

(source)

DANN

Benign

0.72

PhyloP100

1.0

PromoterAI

-0.055

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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