chr3-105864195-T-C

Variant names:

• chr3-105864195-T-C
• rs6804152
• NM_170662.5:c.168+3215A>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.168+3215A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,096 control chromosomes in the GnomAD database, including 4,570 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 0.24 (4570 hom., cov: 31)
• Consequence: CBLB NM_170662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLB	NM_170662.5	c.168+3215A>G		intron_variant	Intron 2 of 18	ENST00000394030.8	NP_733762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLB	ENST00000394030.8	c.168+3215A>G		intron_variant	Intron 2 of 18	1	NM_170662.5	ENSP00000377598.4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35945 AN: 151978 Hom.: 4555 Cov.: 31

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.237 AC: 35997 AN: 152096 Hom.: 4570 Cov.: 31 AF XY: 0.241 AC XY: 17889 AN XY: 74352

African (AFR) AF: 0.293 AC: 12142 AN: 41474

American (AMR) AF: 0.237 AC: 3622 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3468

East Asian (EAS) AF: 0.474 AC: 2452 AN: 5168

South Asian (SAS) AF: 0.239 AC: 1152 AN: 4812

European-Finnish (FIN) AF: 0.224 AC: 2375 AN: 10592

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12998 AN: 67986

Other (OTH) AF: 0.218 AC: 461 AN: 2114

Alfa AF: 0.219 Hom.: 518

Bravo AF: 0.244

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.0
DANN	Benign	0.70
PhyloP100		-0.0040
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: rs6804152; hg19: chr3-105583039;