19-1209715-C-G

Variant names:

• chr19-1209715-C-G
• rs8111699
• NM_000455.5:c.290+2512C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000455.5(STK11):​c.290+2512C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,940 control chromosomes in the GnomAD database, including 22,805 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22805 hom., cov: 31)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488
• Publications: 19 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Genomics England PanelApp, G2P
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5	c.290+2512C>G		intron_variant	Intron 1 of 9	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.290+2512C>G		intron_variant	Intron 1 of 8		NP_001394184.1
STK11	NR_176325.1	n.1426+2512C>G		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.290+2512C>G		intron_variant	Intron 1 of 9	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.290+2512C>G		intron_variant	Intron 1 of 8			ENSP00000498804.1
STK11	ENST00000585748.3	c.-82-8702C>G		intron_variant	Intron 3 of 11	3		ENSP00000477641.2
STK11	ENST00000593219.6	n.290+2512C>G		intron_variant	Intron 1 of 10	3		ENSP00000466610.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81308 AN: 151822 Hom.: 22769 Cov.: 31

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.528

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.536 AC: 81410 AN: 151940 Hom.: 22805 Cov.: 31 AF XY: 0.543 AC XY: 40291 AN XY: 74260

African (AFR) AF: 0.630 AC: 26076 AN: 41396

American (AMR) AF: 0.513 AC: 7829 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1475 AN: 3472

East Asian (EAS) AF: 0.982 AC: 5093 AN: 5184

South Asian (SAS) AF: 0.624 AC: 2995 AN: 4800

European-Finnish (FIN) AF: 0.481 AC: 5080 AN: 10554

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31118 AN: 67954

Other (OTH) AF: 0.534 AC: 1126 AN: 2110

Alfa AF: 0.334 Hom.: 832

Bravo AF: 0.540

Asia WGS AF: 0.798 AC: 2772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.9
DANN	Benign	0.71
PhyloP100		0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8111699; hg19: chr19-1209714;