Variant rs3772534 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_170662.5(CBLB):c.1863G>A(p.Ala621Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,614,090 control chromosomes in the GnomAD database, including 1,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.022 ( 87 hom., cov: 30)

Exomes 𝑓: 0.030 ( 1088 hom. )

Consequence

CBLB
NM_170662.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.17

Variant links:

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 links:

CBLB (HGNC:):

CBLB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 3-105702190-C-T is Benign according to our data. Variant chr3-105702190-C-T is described in ClinVar as [Benign]. Clinvar id is 3060876.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-105702190-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBLB	NM_170662.5 linkuse as main transcript	c.1863G>A	p.Ala621Ala	synonymous_variant	12/19	ENST00000394030.8	NP_733762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBLB	ENST00000394030.8 linkuse as main transcript	c.1863G>A	p.Ala621Ala	synonymous_variant	12/19	1	NM_170662.5	ENSP00000377598.4		Q13191-1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3397

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00471

Gnomad AMI

AF:

0.0802

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0634

Gnomad FIN

AF:

0.00500

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0248

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0312

AC:

7833

AN:

251182

Hom.:

260

AF XY:

0.0329

AC XY:

4469

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.00801

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.0679

Gnomad FIN exome

AF:

0.00577

Gnomad NFE exome

AF:

0.0239

Gnomad OTH exome

AF:

0.0330

GnomAD4 exome

AF:

0.0299

AC:

43691

AN:

1461860

Hom.:

1088

Cov.:

AF XY:

0.0310

AC XY:

22558

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00385

Gnomad4 AMR exome

AF:

0.00937

Gnomad4 ASJ exome

AF:

0.0178

Gnomad4 EAS exome

AF:

0.135

Gnomad4 SAS exome

AF:

0.0675

Gnomad4 FIN exome

AF:

0.00592

Gnomad4 NFE exome

AF:

0.0261

Gnomad4 OTH exome

AF:

0.0332

GnomAD4 genome

AF:

0.0223

AC:

3397

AN:

152230

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

1663

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00470

Gnomad4 AMR

AF:

0.0212

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.0641

Gnomad4 FIN

AF:

0.00500

Gnomad4 NFE

AF:

0.0247

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0230

Hom.:

Bravo

AF:

0.0231

Asia WGS

AF:

0.107

AC:

372

AN:

3478

EpiCase

AF:

0.0251

EpiControl

AF:

0.0235

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CBLB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.22

DANN

Benign

0.46

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over