chr3-105658671-C-T

Position:

• chr3-105658671-C-T

Variant summary

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

The NM_170662.5(CBLB):​c.*299G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 438,350 control chromosomes in the GnomAD database, including 14,873 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 0.26 (5218 hom., cov: 32)
  • Exomes 𝑓: 0.25 (9655 hom.)
• Consequence: CBLB NM_170662.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570

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=-0.41).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBLB	NM_170662.5	c.*299G>A		3_prime_UTR_variant	19/19	ENST00000394030.8	NP_733762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBLB	ENST00000394030	c.*299G>A		3_prime_UTR_variant	19/19	1	NM_170662.5	ENSP00000377598.4

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39225 AN: 152032 Hom.: 5210 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.252 AC: 72234 AN: 286200 Hom.: 9655 Cov.: 2 AF XY: 0.248 AC XY: 36258 AN XY: 146352

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.258 AC: 39249 AN: 152150 Hom.: 5218 Cov.: 32 AF XY: 0.261 AC XY: 19450 AN XY: 74386

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.216

Alfa AF: 0.249 Hom.: 9134

Bravo AF: 0.251

Asia WGS AF: 0.168 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.8
DANN	Benign	0.75

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: rs1042852; hg19: chr3-105377515;