Genetic Variant NM_000455.5:c.862+206C>T (chr19-1221546-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000455.5(STK11):c.862+206C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 783,802 control chromosomes in the GnomAD database, including 26,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4463 hom., cov: 33)

Exomes 𝑓: 0.25 ( 21659 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.65

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 19-1221546-C-T is Benign according to our data. Variant chr19-1221546-C-T is described in ClinVar as [Benign]. Clinvar id is 1224226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5 link	c.862+206C>T	intron_variant	Intron 6 of 9	ENST00000326873.12	NP_000446.1	Q15831-1A0A0S2Z4D1
STK11	NM_001407255.1 link	c.862+206C>T	intron_variant	Intron 6 of 8		NP_001394184.1
STK11	NR_176325.1 link	n.2129+206C>T	intron_variant	Intron 7 of 10

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
STK11	ENST00000326873.12 link	c.862+206C>T	intron_variant	Intron 6 of 9	1	NM_000455.5	ENSP00000324856.6	Q15831-1
STK11	ENST00000652231.1 link	c.862+206C>T	intron_variant	Intron 6 of 8			ENSP00000498804.1	Q15831-2
STK11	ENST00000585748.3 link	c.490+206C>T	intron_variant	Intron 8 of 11	3		ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35889

AN:

151976

Hom.:

4454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.522

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:

0.251

AC:

158763

AN:

631708

Hom.:

21659

Cov.:

AF XY:

0.252

AC XY:

80880

AN XY:

320508

show subpopulations

Gnomad4 AFR exome

AF:

0.196

Gnomad4 AMR exome

AF:

0.267

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.548

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.248

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.236

AC:

35933

AN:

152094

Hom.:

4463

Cov.:

AF XY:

0.241

AC XY:

17904

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.522

Gnomad4 SAS

AF:

0.291

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.209

Hom.:

424

Bravo

AF:

0.236

Asia WGS

AF:

0.420

AC:

1460

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.85

DANN

Benign

0.46

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