rs741765

Variant names:

• chr19-1221546-C-T
• rs741765
• NM_000455.5:c.862+206C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-1221546-C-T
• chr19-1221546-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.65
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• familial pancreatic carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Peutz-Jeghers syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000455.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	NM_000455.5	MANE Select	c.862+206C>T		intron	N/A	NP_000446.1	A0A0S2Z4D1
	STK11	NM_001407255.1		c.862+206C>T		intron	N/A	NP_001394184.1	Q15831-2
	STK11	NR_176325.1		n.2129+206C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.862+206C>T		intron	N/A	ENSP00000324856.6	Q15831-1
	STK11	ENST00000652231.1		c.862+206C>T		intron	N/A	ENSP00000498804.1	Q15831-2
	STK11	ENST00000585748.3	TSL:3	c.490+206C>T		intron	N/A	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35889 AN: 151976 Hom.: 4454 Cov.: 33

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.: 8 AF XY: 0.252 AC XY: 80880 AN XY: 320508

African (AFR) AF: 0.196 AC: 3108 AN: 15822

American (AMR) AF: 0.267 AC: 4892 AN: 18350

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 3429 AN: 14408

East Asian (EAS) AF: 0.548 AC: 17195 AN: 31364

South Asian (SAS) AF: 0.289 AC: 13230 AN: 45814

European-Finnish (FIN) AF: 0.248 AC: 7190 AN: 28962

Middle Eastern (MID) AF: 0.303 AC: 709 AN: 2338

European-Non Finnish (NFE) AF: 0.228 AC: 100884 AN: 442862

Other (OTH) AF: 0.256 AC: 8126 AN: 31788

GnomAD4 genome AF: 0.236 AC: 35933 AN: 152094 Hom.: 4463 Cov.: 33 AF XY: 0.241 AC XY: 17904 AN XY: 74352

African (AFR) AF: 0.202 AC: 8395 AN: 41508

American (AMR) AF: 0.258 AC: 3936 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3470

East Asian (EAS) AF: 0.522 AC: 2685 AN: 5142

South Asian (SAS) AF: 0.291 AC: 1406 AN: 4824

European-Finnish (FIN) AF: 0.249 AC: 2637 AN: 10594

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15256 AN: 67964

Other (OTH) AF: 0.250 AC: 527 AN: 2108

Alfa AF: 0.209 Hom.: 424

Bravo AF: 0.236

Asia WGS AF: 0.420 AC: 1460 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.85
DANN	Benign	0.46
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs741765; hg19: chr19-1221545;