11-119206371-T-TCGAGC

Position:

• chr11-119206371-T-TCGAGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.499

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]

ACMG classification

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	c.-39_-35dup		5_prime_UTR_variant	1/16	ENST00000264033.6

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 304 AN: 151196 Hom.: 1 Cov.: 32

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: 42 AN: 69712 Hom.: 0 AF XY: 0.000569 AC XY: 22 AN XY: 38694

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.: 3 Cov.: 20 AF XY: 0.00101 AC XY: 628 AN XY: 619770

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.: 1 Cov.: 32 AF XY: 0.00243 AC XY: 180 AN XY: 73970

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.: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs759977063; hg19: chr11-119077081;