rs7649466

Variant names:

• chr3-105869001-C-A
• rs7649466
• NM_170662.5:c.-280G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-105869001-C-A
• chr3-105869001-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_170662.5(CBLB):​c.-280G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,054,834 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: CBLB NM_170662.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 13 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)

ENSG00000288848 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170662.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLB	NM_170662.5	MANE Select	c.-280G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_733762.2
	CBLB	NM_170662.5	MANE Select	c.-280G>T		5_prime_UTR	Exon 1 of 19	NP_733762.2
	CBLB	NM_001321788.2		c.-104G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001308717.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLB	ENST00000394030.8	TSL:1 MANE Select	c.-280G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	ENSP00000377598.4
	CBLB	ENST00000394030.8	TSL:1 MANE Select	c.-280G>T		5_prime_UTR	Exon 1 of 19	ENSP00000377598.4
	CBLB	ENST00000405772.5	TSL:2	c.-280G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000384938.1

Frequencies

GnomAD3 genomes AF: 0.000106 AC: 16 AN: 150742 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00299

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000481

GnomAD4 exome AF: 0.0000111 AC: 10 AN: 903966 Hom.: 0 Cov.: 30 AF XY: 0.0000141 AC XY: 6 AN XY: 424292

African (AFR) AF: 0.00 AC: 0 AN: 16068

American (AMR) AF: 0.00 AC: 0 AN: 2246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6510

East Asian (EAS) AF: 0.00195 AC: 8 AN: 4106

South Asian (SAS) AF: 0.00 AC: 0 AN: 31886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1898

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 806034

Other (OTH) AF: 0.0000645 AC: 2 AN: 30992

GnomAD4 genome AF: 0.000106 AC: 16 AN: 150868 Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 9 AN XY: 73706

African (AFR) AF: 0.00 AC: 0 AN: 41352

American (AMR) AF: 0.00 AC: 0 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00300 AC: 15 AN: 5004

South Asian (SAS) AF: 0.00 AC: 0 AN: 4716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67520

Other (OTH) AF: 0.000476 AC: 1 AN: 2102

Alfa AF: 0.00 Hom.: 89

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	17
DANN	Benign	0.93
PhyloP100		0.032
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7649466; hg19: chr3-105587845;