rs2028597

chr3-105839993-G-Achr3-105839993-G-C

Variant summary

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

The NM_170662.5(CBLB):c.419+13421C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 152,172 control chromosomes in the GnomAD database, including 584 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 0.075 (584 hom., cov: 33)
• Consequence: CBLB NM_170662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLB	NM_170662.5	c.419+13421C>T		intron_variant		ENST00000394030.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLB	ENST00000394030.8	c.419+13421C>T		intron_variant		1	NM_170662.5	P1

Frequencies

GnomAD3 genomes AF: 0.0746 AC: 11350 AN: 152054 Hom.: 584 Cov.: 33

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0746

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0804

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.0746 AC: 11349 AN: 152172 Hom.: 584 Cov.: 33 AF XY: 0.0770 AC XY: 5728 AN XY: 74390

Gnomad4 AFR AF: 0.0308

Gnomad4 AMR AF: 0.0744

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0770

Gnomad4 NFE AF: 0.0804

Gnomad4 OTH AF: 0.0805

Alfa AF: 0.0796 Hom.: 389

Bravo AF: 0.0750

Asia WGS AF: 0.170 AC: 589 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.6
Dann	Benign	0.69

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: rs2028597; hg19: chr3-105558837;