Variant chr11-119206371-T-TCGAGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_005188.4(CBL):c.-39_-35dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,412,592 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

CBL
NM_005188.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.499

Variant links:

Genes affected

CBL (HGNC:1541): (Cbl proto-oncogene) This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia, and expansion of CGG repeats in the 5' UTR has been associated with Jacobsen syndrome. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Jul 2016]

CBL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 11-119206371-T-TCGAGC is Benign according to our data. Variant chr11-119206371-T-TCGAGC is described in ClinVar as [Benign]. Clinvar id is 1291108.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00201 (304/151312) while in subpopulation NFE AF= 0.00181 (122/67572). AF 95% confidence interval is 0.00154. There are 1 homozygotes in gnomad4. There are 180 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 304 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBL	NM_005188.4 linkuse as main transcript	c.-39_-35dup		5_prime_UTR_variant	1/16	ENST00000264033.6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
CBL	ENST00000264033.6 linkuse as main transcript	c.-39_-35dup	5_prime_UTR_variant	1/16	1	NM_005188.4	P2
CBL	ENST00000634586.1 linkuse as main transcript	c.-39_-35dup	5_prime_UTR_variant	1/18	5
CBL	ENST00000634840.1 linkuse as main transcript	c.-39_-35dup	5_prime_UTR_variant	1/15	5		A2
CBL	ENST00000700472.1 linkuse as main transcript	c.-39_-35dup	5_prime_UTR_variant, NMD_transcript_variant	1/16

Frequencies

GnomAD3 genomes

AF:

0.00201

AC:

304

AN:

151196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000635

Gnomad FIN

AF:

0.0166

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00181

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000602

AC:

AN:

69712

Hom.:

AF XY:

0.000569

AC XY:

AN XY:

38694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000714

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000775

Gnomad FIN exome

AF:

0.00667

Gnomad NFE exome

AF:

0.000640

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00101

AC:

1269

AN:

1261280

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

628

AN XY:

619770

show subpopulations

Gnomad4 AFR exome

AF:

0.0000387

Gnomad4 AMR exome

AF:

0.000159

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000176

Gnomad4 FIN exome

AF:

0.0143

Gnomad4 NFE exome

AF:

0.000735

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00201

AC:

304

AN:

151312

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

180

AN XY:

73970

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000635

Gnomad4 FIN

AF:

0.0166

Gnomad4 NFE

AF:

0.00181

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00242

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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