Variant rs34928889 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: -0.814

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	MANE
STK11	NM_000455.5 linkuse as main transcript	c.375-49G>A	intron_variant	ENST00000326873.12
STK11	NM_001407255.1 linkuse as main transcript	c.375-49G>A	intron_variant
STK11	NR_176325.1 linkuse as main transcript	n.1642-49G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12 linkuse as main transcript	c.375-49G>A		intron_variant		1	NM_000455.5	P1	Q15831-1

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69479

AN:

151980

Hom.:

16466

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.451

AC XY:

310503

AN XY:

689184

show subpopulations

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.:

AF XY:

0.463

AC XY:

34395

AN XY:

74358

show subpopulations

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:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over