rs6791765

Variant names:

• chr3-105825192-T-C
• rs6791765
• NM_170662.5:c.419+28222A>G

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+28222A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0934 in 152,182 control chromosomes in the GnomAD database, including 743 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 0.093 (743 hom., cov: 32)
• Consequence: CBLB NM_170662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 9 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 (AMR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLB	NM_170662.5	c.419+28222A>G		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+28222A>G		intron_variant	Intron 3 of 18	1	NM_170662.5	ENSP00000377598.4

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14185 AN: 152064 Hom.: 739 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.00982

Gnomad SAS AF: 0.0726

Gnomad FIN AF: 0.0942

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.0934 AC: 14207 AN: 152182 Hom.: 743 Cov.: 32 AF XY: 0.0936 AC XY: 6963 AN XY: 74400

African (AFR) AF: 0.110 AC: 4549 AN: 41518

American (AMR) AF: 0.126 AC: 1925 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3470

East Asian (EAS) AF: 0.00984 AC: 51 AN: 5184

South Asian (SAS) AF: 0.0731 AC: 353 AN: 4830

European-Finnish (FIN) AF: 0.0942 AC: 998 AN: 10596

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0876 AC: 5958 AN: 67998

Other (OTH) AF: 0.0806 AC: 170 AN: 2110

Alfa AF: 0.0881 Hom.: 1093

Bravo AF: 0.0964

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.60
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6791765; hg19: chr3-105544036;