Genetic Variant STK11:c.862+145C>T (chr19-1221485-C-T) – ACMG Classification: Benign (-20 pts)

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.862+145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,295,684 control chromosomes in the GnomAD database, including 39,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4449 hom., cov: 33)

Exomes 𝑓: 0.24 ( 34832 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.96

Publications

6 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=-0.93).

BP6

Variant 19-1221485-C-T is Benign according to our data. Variant chr19-1221485-C-T is described in ClinVar as Benign. ClinVar VariationId is 1245827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
STK11	NM_000455.5 link	c.862+145C>T	intron_variant	Intron 6 of 9	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1 link	c.862+145C>T	intron_variant	Intron 6 of 8		NP_001394184.1
STK11	NR_176325.1 link	n.2129+145C>T	intron_variant	Intron 7 of 10

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
STK11	ENST00000326873.12 link	c.862+145C>T	intron_variant	Intron 6 of 9	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1 link	c.862+145C>T	intron_variant	Intron 6 of 8			ENSP00000498804.1
STK11	ENST00000585748.3 link	c.490+145C>T	intron_variant	Intron 8 of 11	3		ENSP00000477641.2
STK11	ENST00000593219.6 link	n.*687+145C>T	intron_variant	Intron 7 of 10	3		ENSP00000466610.1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35846

AN:

151928

Hom.:

4440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.518

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.244

GnomAD4 exome

AF:

0.237

AC:

271320

AN:

1143638

Hom.:

34832

Cov.:

AF XY:

0.239

AC XY:

133198

AN XY:

557664

show subpopulations

African (AFR)

AF:

0.194

AC:

4924

AN:

25386

American (AMR)

AF:

0.267

AC:

5348

AN:

20066

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

4237

AN:

17932

East Asian (EAS)

AF:

0.544

AC:

18407

AN:

33842

South Asian (SAS)

AF:

0.288

AC:

16888

AN:

58552

European-Finnish (FIN)

AF:

0.249

AC:

7413

AN:

29750

Middle Eastern (MID)

AF:

0.305

AC:

1020

AN:

3340

European-Non Finnish (NFE)

AF:

0.222

AC:

200878

AN:

906146

Other (OTH)

AF:

0.251

AC:

12205

AN:

48624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

9572

19144

28715

38287

47859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7132

14264

21396

28528

35660

<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:

0.236

AC:

35890

AN:

152046

Hom.:

4449

Cov.:

AF XY:

0.241

AC XY:

17886

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.202

AC:

8391

AN:

41474

American (AMR)

AF:

0.257

AC:

3934

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

802

AN:

3466

East Asian (EAS)

AF:

0.519

AC:

2659

AN:

5128

South Asian (SAS)

AF:

0.292

AC:

1407

AN:

4826

European-Finnish (FIN)

AF:

0.249

AC:

2643

AN:

10598

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15240

AN:

67952

Other (OTH)

AF:

0.249

AC:

526

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1395

2789

4184

5578

6973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<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:

0.226

Hom.:

5928

Bravo

AF:

0.235

Asia WGS

AF:

0.419

AC:

1459

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Jun 22, 2018

GeneDx

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

-0.93

CADD

Benign

1.5

(source)

DANN

Benign

0.48

PhyloP100

-3.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over