NM_000455.5:c.290+36G>T

Variant names:

• chr19-1207239-G-T
• rs3764640
• NM_000455.5:c.290+36G>T

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -16 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_StrongBP6_Strong

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 cumulative frequency of 0.246 (AC=384,650) in the gnomAD database across 1,561,928 control chromosomes, including 53,360 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.704. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5916 hom., cov: 32)
  • Exomes 𝑓: 0.24 (47444 hom.)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.01
• Publications: 44 publications found

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, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -16 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BP6Reputable source reports benign		ClinVar 2-star benign — strong (BP6); ClinVar submissions overwhelmingly benign (≥10 total, ≥80% B/LB, <10% P/LP) — strong (BP6, count-based); ClinVar germline classification: Benign/Likely Benign, 2 star(s). ClinVar submissions strongly and reliably favor benignity (10/10 total B/LB).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.7035 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000455.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	STK11 NM_000455.5	MANE Select	c.290+36G>T	intron	Intron 1 of 9	Prot: NP_000446.1 UniProt:
	STK11 NM_001407255.1		c.290+36G>T	intron	Intron 1 of 8	Prot: NP_001394184.1 UniProt:
	STK11 NR_176325.1		n.1426+36G>T	intron	Intron 1 of 10	Prot:

STK11 NM_000455.5

MANE Select

HGVSc / HGVSpc.290+36G>T

Exon rankIntron 1 of 9

intron

Prot: NP_000446.1UniProt: Q15831-1A0A0S2Z4D1

STK11 NM_001407255.1

HGVSc / HGVSpc.290+36G>T

Exon rankIntron 1 of 8

intron

Prot: NP_001394184.1UniProt: Q15831-2

STK11 NR_176325.1

HGVSc / HGVSpn.1426+36G>T

Exon rankIntron 1 of 10

intron

Prot:

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	STK11 ENST00000326873.12	TSL:1MANE Select	c.290+36G>T	intron	Intron 1 of 9	Prot: ENSP00000324856.6 UniProt:
	STK11 ENST00000652231.1		c.290+36G>T	intron	Intron 1 of 8	Prot: ENSP00000498804.1 UniProt:
	STK11 ENST00000585748.3	TSL:3	c.-82-11178G>T	intron	Intron 3 of 11	Prot: ENSP00000477641.2 UniProt:

STK11 ENST00000326873.12

TSL:1MANE Select

HGVSc / HGVSpc.290+36G>T

Exon rankIntron 1 of 9

intron

Prot: ENSP00000324856.6UniProt: Q15831-1

STK11 ENST00000652231.1

HGVSc / HGVSpc.290+36G>T

Exon rankIntron 1 of 8

intron

Prot: ENSP00000498804.1UniProt: Q15831-2

STK11 ENST00000585748.3

TSL:3

HGVSc / HGVSpc.-82-11178G>T

Exon rankIntron 3 of 11

intron

Prot: ENSP00000477641.2UniProt: A0A087WT72

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.265	AC:40211	Hom:5898	AN:151928	Cov:32
GnomAD2 exomes	AF: 0.292	AC:50356	Hom:	AN:172400	Cov:
GnomAD4 exome	AF: 0.244	AC:344372	Hom:47444	AN:1409882	Cov:33
GnomAD4 genome	AF: 0.265	AC:40278	Hom:5916	AN:152046	Cov:32
TOPMed (Bravo)	AF: 0.266	AC:70289	Hom:10334	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.242	AC:72892	Hom:9356	AN:301002	Cov:
Local & regional cohorts 11 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.260	AC:608	Hom:90	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.656	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.230	AC:69	Hom:	AN:300	Cov:
ESP6500 (Exome Variant Server)	AF: 0.230	AC:2812	Hom:	AN:12252	Cov:
GenomeAsia100K	AF: 0.497	AC:1730	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.692	AC:5001	Hom:	AN:7230	Cov:
Qatari Genome	AF: 0.347	AC:61	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.742	AC:90527	Hom:33631	AN:122076	Cov:
Turkish Variome	AF: 0.310	AC:2017	Hom:349	AN:6514	Cov:
UK10K	AF: 0.212	AC:1603	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.672	AC:6025	Hom:2028	AN:8960	Cov:

Showing 17 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
BipEx(Bipolar disorder (including schizoaffective))	0.224	6364	28420	0.224	6463	28844
SCHEMA(Schizophrenia)	0.254	18466	72766	0.234	29816	127250

Showing 2 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	2	Peutz-Jeghers syndrome (2)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	9.0
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.72
GPN-Star LLR	N/A	0.47
GPN-Star score	N/A	-0.47
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	1.0
PromoterAI	N/A	-0.055	Neutral
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.2

Showing 11 of 11 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs3764640;

hg19: chr19-1207238;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar