19-1209715-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
STK11	NM_000455.5	c.290+2512C>G		intron_variant		ENST00000326873.12
STK11	NM_001407255.1	c.290+2512C>G		intron_variant
STK11	NR_176325.1	n.1426+2512C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12	c.290+2512C>G		intron_variant		1	NM_000455.5	P1

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

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.534

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs8111699; hg19: chr19-1209714;