chr19-1228413-AAAGCTTGGG-A

Position:

• chr19-1228413-AAAGCTTGGG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000455.5(STK11):​c.*846_*854delGAAGCTTGG variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 225,774 control chromosomes in the GnomAD database, including 173 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (118 hom., cov: 32)
  • Exomes 𝑓: 0.034 (55 hom.)
• Consequence: STK11 NM_000455.5 splice_region
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.35

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]

CBARP (HGNC:28617): (CACN subunit beta associated regulatory protein) Predicted to enable transmembrane transporter binding activity. Predicted to be involved in negative regulation of calcium ion-dependent exocytosis and negative regulation of voltage-gated calcium channel activity. Predicted to be located in synaptic vesicle membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Predicted to colocalize with growth cone and secretory granule. [provided by Alliance of Genome Resources, Apr 2022]

STK11 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-1228413-AAAGCTTGGG-A is Benign according to our data. Variant chr19-1228413-AAAGCTTGGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 328247.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0294 (4477/152282) while in subpopulation NFE AF= 0.0486 (3305/68000). AF 95% confidence interval is 0.0472. There are 118 homozygotes in gnomad4. There are 2028 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4477 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK11	NM_000455.5	c.*846_*854delGAAGCTTGG		splice_region_variant	10/10	ENST00000326873.12	NP_000446.1
CBARP	NM_001393918.1	c.*757_*765delCCCAAGCTT		3_prime_UTR_variant	10/10	ENST00000650044.2	NP_001380847.1
STK11	NM_000455.5	c.*846_*854delGAAGCTTGG		3_prime_UTR_variant	10/10	ENST00000326873.12	NP_000446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.*846_*854delGAAGCTTGG		splice_region_variant	10/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000585748.3	c.*846_*854delGAAGCTTGG		splice_region_variant	12/12	3		ENSP00000477641.2
CBARP	ENST00000650044	c.*757_*765delCCCAAGCTT		3_prime_UTR_variant	10/10		NM_001393918.1	ENSP00000497208.1
STK11	ENST00000326873.12	c.*846_*854delGAAGCTTGG		3_prime_UTR_variant	10/10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000585748.3	c.*846_*854delGAAGCTTGG		3_prime_UTR_variant	12/12	3		ENSP00000477641.2

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4477 AN: 152168 Hom.: 118 Cov.: 32

Gnomad AFR AF: 0.00895

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0230

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0486

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0337 AC: 2479 AN: 73492 Hom.: 55 AF XY: 0.0345 AC XY: 1175 AN XY: 34030

Gnomad4 AFR exome AF: 0.00912

Gnomad4 AMR exome AF: 0.0222

Gnomad4 ASJ exome AF: 0.0259

Gnomad4 EAS exome AF: 0.00178

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0455

Gnomad4 OTH exome AF: 0.0305

GnomAD4 genome AF: 0.0294 AC: 4477 AN: 152282 Hom.: 118 Cov.: 32 AF XY: 0.0272 AC XY: 2028 AN XY: 74464

Gnomad4 AFR AF: 0.00893

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.0230

Gnomad4 NFE AF: 0.0486

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0365 Hom.: 15

Bravo AF: 0.0285

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Peutz-Jeghers syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs142990629; hg19: chr19-1228412;