Variant chr3-105685454-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_170662.5(CBLB):c.2067G>A(p.Pro689=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00677 in 1,612,824 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 58 hom. )

Consequence

CBLB
NM_170662.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.119

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 3-105685454-C-T is Benign according to our data. Variant chr3-105685454-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00694 (10133/1460616) while in subpopulation MID AF= 0.0184 (106/5764). AF 95% confidence interval is 0.0156. There are 58 homozygotes in gnomad4_exome. There are 4933 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBLB	NM_170662.5 linkuse as main transcript	c.2067G>A	p.Pro689=	synonymous_variant	14/19	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.2067G>A	p.Pro689=	synonymous_variant	14/19	1	NM_170662.5	ENSP00000377598	P1	Q13191-1

Frequencies

GnomAD3 genomes

AF:

0.00515

AC:

784

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00457

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00785

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00508

AC:

1274

AN:

250732

Hom.:

AF XY:

0.00526

AC XY:

713

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00602

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00226

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00719

Gnomad OTH exome

AF:

0.00670

GnomAD4 exome

AF:

0.00694

AC:

10133

AN:

1460616

Hom.:

Cov.:

AF XY:

0.00679

AC XY:

4933

AN XY:

726658

show subpopulations

Gnomad4 AFR exome

AF:

0.000897

Gnomad4 AMR exome

AF:

0.00597

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00227

Gnomad4 FIN exome

AF:

0.000618

Gnomad4 NFE exome

AF:

0.00792

Gnomad4 OTH exome

AF:

0.00674

GnomAD4 genome

AF:

0.00515

AC:

784

AN:

152208

Hom.:

Cov.:

AF XY:

0.00481

AC XY:

358

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00193

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00457

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00785

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00708

Hom.:

Bravo

AF:

0.00554

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0105

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	CBLB: BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 13, 2018	- -

CBLB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 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

-0.33

CADD

Benign

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: -20

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