7-107755460-C-T

Variant summary

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

The NM_024814.4(CBLL1):​c.409C>T​(p.His137Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 1,586,364 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CBLL1
NM_024814.4 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.23
Variant links:
Genes affected
CBLL1 (HGNC:21225): (Cbl proto-oncogene like 1) This gene encodes an E3 ubiquitin-ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation. A related pseudogene has been identified on chromosome X. Alternative splicing results in a non-coding transcript variant. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CBLL1NM_024814.4 linkc.409C>T p.His137Tyr missense_variant Exon 5 of 6 ENST00000440859.8 NP_079090.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CBLL1ENST00000440859.8 linkc.409C>T p.His137Tyr missense_variant Exon 5 of 6 1 NM_024814.4 ENSP00000401277.2 Q75N03-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151502
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000485
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.97e-7
AC:
1
AN:
1434862
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
713862
show subpopulations
Gnomad4 AFR exome
AF:
0.0000313
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
AF:
0.0000132
AC:
2
AN:
151502
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74008
show subpopulations
Gnomad4 AFR
AF:
0.0000485
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.409C>T (p.H137Y) alteration is located in exon 5 (coding exon 5) of the CBLL1 gene. This alteration results from a C to T substitution at nucleotide position 409, causing the histidine (H) at amino acid position 137 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
24
DANN
Benign
0.96
DEOGEN2
Benign
0.082
T;.;T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.43
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;.;.
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-0.86
N;N;N
REVEL
Benign
0.28
Sift
Benign
0.40
T;T;T
Sift4G
Benign
0.59
T;T;T
Polyphen
0.99
D;.;.
Vest4
0.70
MutPred
0.29
Loss of disorder (P = 0.0655);.;.;
MVP
0.76
MPC
1.0
ClinPred
0.80
D
GERP RS
5.8
Varity_R
0.15
gMVP
0.77

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.

Other links and lift over

dbSNP: rs1477757302; hg19: chr7-107395905; API