Genetic Variant STK11:c.464+10C>T (chr19-1219423-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_StrongBS1BS2

The NM_000455.5(STK11):c.464+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 756,952 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000043 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -0.413

Publications

0 publications found

Variant links:

COSMIC-nc: COSV104641678

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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet
familial ovarian cancer
Inheritance: Unknown 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=-0.8).

BP6

Variant 19-1219423-C-T is Benign according to our data. Variant chr19-1219423-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 142410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000151 (93/617302) while in subpopulation MID AF = 0.00156 (5/3202). AF 95% confidence interval is 0.000627. There are 1 homozygotes in GnomAdExome4. There are 70 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 6 AD,Unknown gene.

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.464+10C>T	intron	N/A	NP_000446.1	A0A0S2Z4D1
STK11	NM_001407255.1		c.464+10C>T	intron	N/A	NP_001394184.1	Q15831-2
STK11	NR_176325.1		n.1731+10C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STK11	ENST00000326873.12	TSL:1 MANE Select	c.464+10C>T	intron	N/A	ENSP00000324856.6	Q15831-1
STK11	ENST00000652231.1		c.464+10C>T	intron	N/A	ENSP00000498804.1	Q15831-2
STK11	ENST00000585748.3	TSL:3	c.92+10C>T	intron	N/A	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes

AF:

0.0000430

AC:

AN:

139534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000521

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000272

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000310

Gnomad OTH

AF:

0.000512

GnomAD2 exomes

AF:

0.000113

AC:

AN:

176780

AF XY:

0.000179

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000149

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000160

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000419

GnomAD4 exome

AF:

0.000151

AC:

AN:

617302

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

AN XY:

322478

show subpopulations

African (AFR)

AF:

0.000131

AC:

AN:

15250

American (AMR)

AF:

0.000159

AC:

AN:

31418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13492

East Asian (EAS)

AF:

0.000236

AC:

AN:

12736

South Asian (SAS)

AF:

0.000800

AC:

AN:

66284

European-Finnish (FIN)

AF:

0.0000339

AC:

AN:

29542

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

3202

European-Non Finnish (NFE)

AF:

0.0000357

AC:

AN:

420594

Other (OTH)

AF:

0.000363

AC:

AN:

24784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000430

AC:

AN:

139650

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

67744

show subpopulations

African (AFR)

AF:

0.0000520

AC:

AN:

38498

American (AMR)

AF:

0.00

AC:

AN:

14202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3292

East Asian (EAS)

AF:

0.000272

AC:

AN:

3672

South Asian (SAS)

AF:

0.00

AC:

AN:

3730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0000310

AC:

AN:

64492

Other (OTH)

AF:

0.000508

AC:

AN:

1968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000509

Hom.:

Bravo

AF:

0.0000340

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Peutz-Jeghers syndrome (6)

Hereditary cancer-predisposing syndrome (2)

not provided (2)

not specified (2)

Breast and/or ovarian cancer (1)

Peutz-Jeghers syndrome;C0235974:Carcinoma of pancreas;C1336708:Germ cell tumor of testis;C1835047:Melanoma, cutaneous malignant, susceptibility to, 1 (1)

STK11-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.9

(source)

DANN

Benign

0.87

PhyloP100

-0.41

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)

0.040

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

Computational scores

Splicing

Publications

Other links and lift over