2-230747515-A-T

Variant names:

• chr2-230747515-A-T
• rs10498255
• NM_016289.4:c.-43-12444A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016289.4(CAB39):​c.-43-12444A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CAB39 NM_016289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904
• Publications: 9 publications found

Genes affected

CAB39 (HGNC:20292): (calcium binding protein 39) Enables kinase binding activity and protein serine/threonine kinase activator activity. Involved in intracellular signal transduction; peptidyl-serine phosphorylation; and positive regulation of protein phosphorylation. Located in extracellular exosome. Implicated in hepatocellular carcinoma. Biomarker of hepatocellular carcinoma and pancreatic cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016289.4. 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
	CAB39	NM_016289.4	MANE Select	c.-43-12444A>T		intron	N/A	NP_057373.1
	CAB39	NM_001130849.2		c.-43-12444A>T		intron	N/A	NP_001124321.1
	CAB39	NM_001130850.2		c.-43-12444A>T		intron	N/A	NP_001124322.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAB39	ENST00000258418.10	TSL:1 MANE Select	c.-43-12444A>T		intron	N/A	ENSP00000258418.5
	CAB39	ENST00000410084.7	TSL:1	c.-43-12444A>T		intron	N/A	ENSP00000386642.3
	CAB39	ENST00000409788.7	TSL:2	c.-43-12444A>T		intron	N/A	ENSP00000386238.3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.9
DANN	Benign	0.78
PhyloP100		0.90

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: rs10498255; hg19: chr2-231612230;