rs2965118

Variant names:

• chr19-44789032-C-G
• rs2965118
• NM_012116.4:c.918-972C>G

Variant summary

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

The NM_012116.4(CBLC):​c.918-972C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,066 control chromosomes in the GnomAD database, including 6,499 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 0.22 (6499 hom., cov: 31)
• Consequence: CBLC NM_012116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLC	NM_012116.4	c.918-972C>G		intron_variant	Intron 5 of 10	ENST00000647358.2	NP_036248.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLC	ENST00000647358.2	c.918-972C>G		intron_variant	Intron 5 of 10		NM_012116.4	ENSP00000494162.1
CBLC	ENST00000341505.4	c.780-972C>G		intron_variant	Intron 4 of 9	1		ENSP00000340250.4
CBLC	ENST00000647063.1	n.*13-972C>G		intron_variant	Intron 4 of 5			ENSP00000495258.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32989 AN: 151948 Hom.: 6466 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0824

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.0436

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.218 AC: 33085 AN: 152066 Hom.: 6499 Cov.: 31 AF XY: 0.215 AC XY: 15958 AN XY: 74356

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0828

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.0436

Gnomad4 NFE AF: 0.0855

Gnomad4 OTH AF: 0.200

Alfa AF: 0.168 Hom.: 506

Bravo AF: 0.235

Asia WGS AF: 0.212 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.36

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: rs2965118; hg19: chr19-45292289;