19-1205638-G-T

Position:

• chr19-1205638-G-T

Variant summary

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

The ENST00000585748.3(STK11):​c.-82-12779G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 151,982 control chromosomes in the GnomAD database, including 2,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.16 (2125 hom., cov: 32)
• Consequence: STK11 ENST00000585748.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.49

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 19-1205638-G-T is Benign according to our data. Variant chr19-1205638-G-T is described in ClinVar as [Benign]. Clinvar id is 1276994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000585748.3	c.-82-12779G>T		intron_variant	Intron 3 of 11	3		ENSP00000477641.2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24243 AN: 151864 Hom.: 2124 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.160 AC: 24247 AN: 151982 Hom.: 2125 Cov.: 32 AF XY: 0.162 AC XY: 12036 AN XY: 74294

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0831 Hom.: 106

Bravo AF: 0.152

Asia WGS AF: 0.217 AC: 755 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Jan 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs74720037; hg19: chr19-1205637;