chr19-1205638-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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000585748.3	c.-82-12779G>T		intron_variant		3		ENSP00000477641

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;