19-1221485-C-T

Position:

• chr19-1221485-C-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.862+145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,295,684 control chromosomes in the GnomAD database, including 39,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4449 hom., cov: 33)
  • Exomes 𝑓: 0.24 (34832 hom.)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.96

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=-0.93).
• BP6: Variant 19-1221485-C-T is Benign according to our data. Variant chr19-1221485-C-T is described in ClinVar as [Benign]. Clinvar id is 1245827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.862+145C>T		intron_variant		ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.862+145C>T		intron_variant			NP_001394184.1
STK11	NR_176325.1	n.2129+145C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.862+145C>T		intron_variant		1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.862+145C>T		intron_variant				ENSP00000498804.1
STK11	ENST00000585748.3	c.490+145C>T		intron_variant		3		ENSP00000477641.2

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35846 AN: 151928 Hom.: 4440 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.237 AC: 271320 AN: 1143638 Hom.: 34832 Cov.: 16 AF XY: 0.239 AC XY: 133198 AN XY: 557664

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.544

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.236 AC: 35890 AN: 152046 Hom.: 4449 Cov.: 33 AF XY: 0.241 AC XY: 17886 AN XY: 74342

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.249

Alfa AF: 0.137 Hom.: 273

Bravo AF: 0.235

Asia WGS AF: 0.419 AC: 1459 AN: 3478

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	Jun 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs741764; hg19: chr19-1221484; COSMIC: COSV58826063; COSMIC: COSV58826063;