chr19-44778140-C-T

Variant names:

• chr19-44778140-C-T
• NM_012116.4:c.209C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012116.4(CBLC):​c.209C>T​(p.Pro70Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CBLC NM_012116.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.564
• Publications: 0 publications found

Genes affected

CBLC (HGNC:15961): (Cbl proto-oncogene C) This gene encodes a member of the Cbl family of E3 ubiquitin ligases. Cbl proteins play important roles in cell signaling through the ubiquitination and subsequent downregulation of tyrosine kinases. Expression of this gene may be restricted to epithelial cells, and alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14668691).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012116.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLC	NM_012116.4	MANE Select	c.209C>T	p.Pro70Leu	missense	Exon 1 of 11	NP_036248.3
	CBLC	NM_001130852.1		c.209C>T	p.Pro70Leu	missense	Exon 1 of 10	NP_001124324.1	Q9ULV8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLC	ENST00000647358.2	MANE Select	c.209C>T	p.Pro70Leu	missense	Exon 1 of 11	ENSP00000494162.1	Q9ULV8-1
	CBLC	ENST00000341505.4	TSL:1	c.209C>T	p.Pro70Leu	missense	Exon 1 of 10	ENSP00000340250.4	Q9ULV8-2
	CBLC	ENST00000880089.1		c.209C>T	p.Pro70Leu	missense	Exon 1 of 12	ENSP00000550148.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.56
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.084
Sift	Benign	0.16	T
Sift4G	Benign	0.14	T
Polyphen		0.0080	B
Vest4		0.18
MutPred		0.40		Loss of glycosylation at P70 (P = 0.0413)
MVP		0.68
MPC		0.33
ClinPred		0.095	T
GERP RS		0.88
PromoterAI		-0.028	Neutral
Varity_R		0.11
gMVP		0.22
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr19-45281397;