rs17280845

Positions:

• chr3-105725692-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170662.5(CBLB):​c.1204-5442G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,982 control chromosomes in the GnomAD database, including 3,826 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 0.21 (3826 hom., cov: 32)
• Consequence: CBLB NM_170662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLB	NM_170662.5	c.1204-5442G>A		intron_variant		ENST00000394030.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLB	ENST00000394030.8	c.1204-5442G>A		intron_variant		1	NM_170662.5	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31992 AN: 151864 Hom.: 3833 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.0865

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.210 AC: 31983 AN: 151982 Hom.: 3826 Cov.: 32 AF XY: 0.205 AC XY: 15246 AN XY: 74254

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.0871

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.230

Alfa AF: 0.267 Hom.: 7368

Bravo AF: 0.204

Asia WGS AF: 0.113 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.74

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: rs17280845; hg19: chr3-105444536;