3-105869001-C-G

Position:

• chr3-105869001-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_170662.5(CBLB):​c.-280G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,054,432 control chromosomes in the GnomAD database, including 16,831 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 0.19 (2663 hom., cov: 32)
  • Exomes 𝑓: 0.18 (14168 hom.)
• Consequence: CBLB NM_170662.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

Genes affected

CBLB (HGNC:1542): (Cbl proto-oncogene B) This gene encodes an E3 ubiquitin-protein ligase which promotes proteosome-mediated protein degradation by transferring ubiquitin from an E2 ubiquitin-conjugating enzyme to a substrate. The encoded protein is involved in the regulation of immune response by limiting T-cell receptor, B-cell receptor, and high affinity immunoglobulin epsilon receptor activation. Studies in mouse suggest that this gene is involved in antifungal host defense and that its inhibition leads to increased fungal killing. Manipulation of this gene may be beneficial in implementing immunotherapies for a variety of conditions, including cancer, autoimmune diseases, allergies, and infections. [provided by RefSeq, Sep 2017]

CBLB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBLB	NM_170662.5	c.-280G>C		5_prime_UTR_variant	1/19	ENST00000394030.8	NP_733762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBLB	ENST00000394030.8	c.-280G>C		5_prime_UTR_variant	1/19	1	NM_170662.5	ENSP00000377598.4

Frequencies

GnomAD3 genomes AF: 0.186 AC: 27974 AN: 150714 Hom.: 2655 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0935

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.177 AC: 159886 AN: 903592 Hom.: 14168 Cov.: 30 AF XY: 0.177 AC XY: 75057 AN XY: 424126

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.186 AC: 28005 AN: 150840 Hom.: 2663 Cov.: 32 AF XY: 0.187 AC XY: 13809 AN XY: 73694

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.170

Alfa AF: 0.0757 Hom.: 89

Bravo AF: 0.190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs7649466; hg19: chr3-105587845;