rs10419669

chr19-44794812-G-Achr19-44794812-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012116.4(CBLC):c.1362+531G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,648 control chromosomes in the GnomAD database, including 2,174 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (2174 hom., cov: 29)
• Consequence: CBLC NM_012116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLC	NM_012116.4	c.1362+531G>A		intron_variant		ENST00000647358.2
CBLC	NM_001130852.1	c.1224+531G>A		intron_variant
CBLC	XM_011526688.3	c.1362+531G>A		intron_variant
CBLC	XM_011526689.3	c.1224+531G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLC	ENST00000647358.2	c.1362+531G>A		intron_variant			NM_012116.4	P1
CBLC	ENST00000341505.4	c.1224+531G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21017 AN: 151530 Hom.: 2155 Cov.: 29

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0805

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.0919

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0725

Gnomad OTH AF: 0.138

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.139 AC: 21091 AN: 151648 Hom.: 2174 Cov.: 29 AF XY: 0.140 AC XY: 10387 AN XY: 74086

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.0804

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.0921

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0725

Gnomad4 OTH AF: 0.140

Alfa AF: 0.0776 Hom.: 865

Bravo AF: 0.142

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	6.0
Dann	Benign	0.83

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

Other links and lift over

dbSNP: rs10419669; hg19: chr19-45298069;