7-107758865-C-T

Variant names:

• chr7-107758865-C-T
• NM_024814.4:c.1163C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024814.4(CBLL1):​c.1163C>T​(p.Pro388Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBLL1 NM_024814.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25389317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLL1	NM_024814.4	c.1163C>T	p.Pro388Leu	missense_variant	Exon 6 of 6	ENST00000440859.8	NP_079090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLL1	ENST00000440859.8	c.1163C>T	p.Pro388Leu	missense_variant	Exon 6 of 6	1	NM_024814.4	ENSP00000401277.2
CBLL1	ENST00000222597.7	c.1160C>T	p.Pro387Leu	missense_variant	Exon 6 of 6	1		ENSP00000222597.2
CBLL1	ENST00000698938.1	c.1199C>T	p.Pro400Leu	missense_variant	Exon 6 of 6			ENSP00000514046.1
CBLL1	ENST00000420796.1	c.*45C>T		downstream_gene_variant		5		ENSP00000410615.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1163C>T (p.P388L) alteration is located in exon 6 (coding exon 6) of the CBLL1 gene. This alteration results from a C to T substitution at nucleotide position 1163, causing the proline (P) at amino acid position 388 to be replaced by a leucine (L). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.056
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.12
Sift	Benign	0.42	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.023	B;.
Vest4		0.54
MutPred		0.21		Loss of glycosylation at P388 (P = 0.0191);.;
MVP		0.44
MPC		0.36
ClinPred		0.58	D
GERP RS		4.0
Varity_R		0.21
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-107399310;