rs552303618

Variant names:

• chr3-105869369-G-A
• NM_001321790.2:c.20C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-105869369-G-A
• chr3-105869369-G-C
• chr3-105869369-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321790.2(CBLB):​c.20C>T​(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000168 in 1,190,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: CBLB NM_001321790.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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]

ENSG00000288848 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07922149).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLB	NM_001321790.2	c.20C>T	p.Pro7Leu	missense_variant	Exon 1 of 18		NP_001308719.1
CBLB	XM_017007395.2	c.20C>T	p.Pro7Leu	missense_variant	Exon 1 of 19		XP_016862884.1
CBLB	XM_017007398.2	c.20C>T	p.Pro7Leu	missense_variant	Exon 1 of 18		XP_016862887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLB	ENST00000438603.6	c.20C>T	p.Pro7Leu	missense_variant	Exon 1 of 4	4		ENSP00000409750.2
CBLB	ENST00000443752.2	c.-15+56C>T		intron_variant	Intron 1 of 3	3		ENSP00000393906.2
CBLB	ENST00000643322.1	n.20C>T		non_coding_transcript_exon_variant	Exon 1 of 21			ENSP00000496352.1
ENSG00000288848	ENST00000690303.2	n.190G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000168 AC: 2 AN: 1190620 Hom.: 0 Cov.: 29 AF XY: 0.00000172 AC XY: 1 AN XY: 582822

Gnomad4 AFR exome AF: 0.0000773

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.84
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.92	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.15
Sift	Benign	0.48	T
MutPred		0.12		Loss of disorder (P = 0.0483);
MVP		0.17
ClinPred		0.15	T
GERP RS		2.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-105588213;