rs730881960

Variant names:

• chr19-1219429-AG-A
• rs730881960
• NM_000455.5:c.464+20delG

Your query was ambiguous. Multiple possible variants found:

• chr19-1219429-AG-A
• chr19-1219429-AG-AGG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000455.5(STK11):​c.464+20delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000902 in 865,172 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000022 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00010 (1 hom.)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.124
• Publications: 0 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Genomics England PanelApp, G2P
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 19-1219429-AG-A is Benign according to our data. Variant chr19-1219429-AG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 182879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000103 (75/726494) while in subpopulation AMR AF = 0.00222 (68/30670). AF 95% confidence interval is 0.00179. There are 1 homozygotes in GnomAdExome4. There are 30 alleles in the male GnomAdExome4 subpopulation. Median coverage is 45. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 75 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	NM_000455.5	MANE Select	c.464+20delG		intron	N/A	NP_000446.1
	STK11	NM_001407255.1		c.464+20delG		intron	N/A	NP_001394184.1
	STK11	NR_176325.1		n.1731+20delG		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.464+17delG		intron	N/A	ENSP00000324856.6
	STK11	ENST00000652231.1		c.464+17delG		intron	N/A	ENSP00000498804.1
	STK11	ENST00000585748.3	TSL:3	c.92+17delG		intron	N/A	ENSP00000477641.2

Frequencies

GnomAD3 genomes AF: 0.0000216 AC: 3 AN: 138678 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000142

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000156

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000376 AC: 64 AN: 170296 AF XY: 0.000317

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000143

Gnomad OTH exome AF: 0.00388

GnomAD4 exome AF: 0.000103 AC: 75 AN: 726494 Hom.: 1 Cov.: 45 AF XY: 0.0000810 AC XY: 30 AN XY: 370290

African (AFR) AF: 0.00 AC: 0 AN: 17146

American (AMR) AF: 0.00222 AC: 68 AN: 30670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14226

East Asian (EAS) AF: 0.00 AC: 0 AN: 13836

South Asian (SAS) AF: 0.00 AC: 0 AN: 68672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3312

European-Non Finnish (NFE) AF: 0.00000192 AC: 1 AN: 520718

Other (OTH) AF: 0.000211 AC: 6 AN: 28490

GnomAD4 genome AF: 0.0000216 AC: 3 AN: 138678 Hom.: 0 Cov.: 34 AF XY: 0.0000149 AC XY: 1 AN XY: 67234

African (AFR) AF: 0.00 AC: 0 AN: 38148

American (AMR) AF: 0.000142 AC: 2 AN: 14036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3280

East Asian (EAS) AF: 0.00 AC: 0 AN: 3572

South Asian (SAS) AF: 0.00 AC: 0 AN: 3694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000156 AC: 1 AN: 64114

Other (OTH) AF: 0.00 AC: 0 AN: 1930

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000680

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Peutz-Jeghers syndrome (3)
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs730881960; hg19: chr19-1219428;