rs2028597

Variant names:

• chr3-105839993-G-A
• rs2028597
• NM_170662.5:c.419+13421C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-105839993-G-A
• chr3-105839993-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 publications found

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 Gene-Disease associations (from GenCC):

• autoimmune disease, multisystem, infantile-onset, 3

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CBLB	NM_170662.5	c.419+13421C>T		intron_variant	Intron 3 of 18	ENST00000394030.8	NP_733762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLB	ENST00000394030.8	c.419+13421C>T		intron_variant	Intron 3 of 18	1	NM_170662.5	ENSP00000377598.4

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

African (AFR) AF: 0.0308 AC: 1278 AN: 41532

American (AMR) AF: 0.0744 AC: 1137 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1502 AN: 5174

South Asian (SAS) AF: 0.112 AC: 540 AN: 4826

European-Finnish (FIN) AF: 0.0770 AC: 813 AN: 10564

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0804 AC: 5465 AN: 68004

Other (OTH) AF: 0.0805 AC: 170 AN: 2112

Alfa AF: 0.0799 Hom.: 534

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
PhyloP100		-0.041
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: rs2028597; hg19: chr3-105558837;