rs34928889

Positions:

• chr19-1219275-G-A
• chr19-1219275-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000455.5(STK11):​c.375-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,548,922 control chromosomes in the GnomAD database, including 162,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16494 hom., cov: 34)
  • Exomes 𝑓: 0.45 (145691 hom.)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:5
• Conservation: PhyloP100: -0.814

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-1219275-G-A is Benign according to our data. Variant chr19-1219275-G-A is described in ClinVar as [Benign]. Clinvar id is 256205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.375-49G>A		intron_variant		ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.375-49G>A		intron_variant			NP_001394184.1
STK11	NR_176325.1	n.1642-49G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.375-49G>A		intron_variant		1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.375-49G>A		intron_variant				ENSP00000498804.1
STK11	ENST00000585748.3	c.3-49G>A		intron_variant		3		ENSP00000477641.2
STK11	ENST00000593219.5	n.*200-49G>A		intron_variant		3		ENSP00000466610.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69479 AN: 151980 Hom.: 16466 Cov.: 34

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.446

GnomAD3 exomes AF: 0.468 AC: 73682 AN: 157324 Hom.: 18358 AF XY: 0.469 AC XY: 39147 AN XY: 83446

Gnomad AFR exome AF: 0.474

Gnomad AMR exome AF: 0.411

Gnomad ASJ exome AF: 0.410

Gnomad EAS exome AF: 0.855

Gnomad SAS exome AF: 0.470

Gnomad FIN exome AF: 0.467

Gnomad NFE exome AF: 0.429

Gnomad OTH exome AF: 0.452

GnomAD4 exome AF: 0.451 AC: 629562 AN: 1396824 Hom.: 145691 Cov.: 30 AF XY: 0.451 AC XY: 310503 AN XY: 689184

Gnomad4 AFR exome AF: 0.468

Gnomad4 AMR exome AF: 0.414

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.859

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.462

GnomAD4 genome AF: 0.457 AC: 69563 AN: 152098 Hom.: 16494 Cov.: 34 AF XY: 0.463 AC XY: 34395 AN XY: 74358

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.452

Alfa AF: 0.426 Hom.: 2992

Bravo AF: 0.457

Asia WGS AF: 0.661 AC: 2297 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Squamous cell lung carcinoma Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing;in vivo

Faculté Pluridciplinaire Nador, Université Mohamed Premier

May 05, 2020

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Hereditary cancer-predisposing syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2014

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Peutz-Jeghers syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs34928889; hg19: chr19-1219274;