rs752145860

Variant names:

• chr19-44781050-C-A
• rs752145860
• NM_012116.4:c.499C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-44781050-C-A
• chr19-44781050-C-G
• chr19-44781050-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_012116.4(CBLC):​c.499C>A​(p.Arg167Arg) variant causes a splice region, synonymous 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBLC NM_012116.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.001041
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=2.58 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLC	NM_012116.4	c.499C>A	p.Arg167Arg	splice_region_variant, synonymous_variant	Exon 2 of 11	ENST00000647358.2	NP_036248.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLC	ENST00000647358.2	c.499C>A	p.Arg167Arg	splice_region_variant, synonymous_variant	Exon 2 of 11		NM_012116.4	ENSP00000494162.1
CBLC	ENST00000341505.4	c.499C>A	p.Arg167Arg	splice_region_variant, synonymous_variant	Exon 2 of 10	1		ENSP00000340250.4
CBLC	ENST00000647063.1	n.124C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 6			ENSP00000495258.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0010
dbscSNV1_RF	Benign	0.078
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

Other links and lift over

dbSNP: rs752145860; hg19: chr19-45284307;