19-1228333-C-G

Variant names:

• chr19-1228333-C-G
• rs886054225
• NM_001393918.1:c.*846G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001393918.1(CBARP):​c.*846G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 252,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: CBARP NM_001393918.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 0 publications found

Genes affected

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: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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393918.1. 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
	CBARP	NM_001393918.1	MANE Select	c.*846G>C		3_prime_UTR	Exon 10 of 10	NP_001380847.1	Q8N350-3
	STK11	NM_000455.5	MANE Select	c.*757C>G		3_prime_UTR	Exon 10 of 10	NP_000446.1	A0A0S2Z4D1
	CBARP	NM_152769.3		c.*2560G>C		3_prime_UTR	Exon 9 of 9	NP_689982.3	Q8N350-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBARP	ENST00000650044.2	MANE Select	c.*846G>C		3_prime_UTR	Exon 10 of 10	ENSP00000497208.1	Q8N350-3
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.*757C>G		3_prime_UTR	Exon 10 of 10	ENSP00000324856.6	Q15831-1
	CBARP	ENST00000590083.5	TSL:1	c.*2560G>C		3_prime_UTR	Exon 9 of 9	ENSP00000465260.1	Q8N350-4

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152246 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000398 AC: 4 AN: 100422 Hom.: 0 Cov.: 4 AF XY: 0.0000640 AC XY: 3 AN XY: 46888

African (AFR) AF: 0.000485 AC: 2 AN: 4126

American (AMR) AF: 0.000409 AC: 1 AN: 2446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5142

East Asian (EAS) AF: 0.00 AC: 0 AN: 11410

South Asian (SAS) AF: 0.00 AC: 0 AN: 1130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 70

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 522

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68258

Other (OTH) AF: 0.000137 AC: 1 AN: 7318

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152364 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74508

African (AFR) AF: 0.000962 AC: 40 AN: 41594

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.61
PhyloP100		-0.21

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: rs886054225; hg19: chr19-1228332;