2-230747515-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016289.4(CAB39):​c.-43-12444A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,216 control chromosomes in the GnomAD database, including 13,509 homozygotes. 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 0.36 (13509 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

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>G		intron	N/A	NP_057373.1
	CAB39	NM_001130849.2		c.-43-12444A>G		intron	N/A	NP_001124321.1
	CAB39	NM_001130850.2		c.-43-12444A>G		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>G		intron	N/A	ENSP00000258418.5
	CAB39	ENST00000410084.7	TSL:1	c.-43-12444A>G		intron	N/A	ENSP00000386642.3
	CAB39	ENST00000409788.7	TSL:2	c.-43-12444A>G		intron	N/A	ENSP00000386238.3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54143 AN: 152098 Hom.: 13461 Cov.: 32

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.356 AC: 54242 AN: 152216 Hom.: 13509 Cov.: 32 AF XY: 0.345 AC XY: 25683 AN XY: 74428

African (AFR) AF: 0.709 AC: 29436 AN: 41514

American (AMR) AF: 0.241 AC: 3686 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1247 AN: 3472

East Asian (EAS) AF: 0.142 AC: 734 AN: 5178

South Asian (SAS) AF: 0.141 AC: 682 AN: 4822

European-Finnish (FIN) AF: 0.157 AC: 1670 AN: 10604

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15769 AN: 68004

Other (OTH) AF: 0.333 AC: 704 AN: 2114

Alfa AF: 0.280 Hom.: 1380

Bravo AF: 0.380

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	7.3
DANN	Benign	0.81
PhyloP100		0.90
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: rs10498255; hg19: chr2-231612230;