chr19-44794812-G-A

Variant names:

• chr19-44794812-G-A
• rs10419669
• NM_012116.4:c.1362+531G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLC	NM_012116.4	MANE Select	c.1362+531G>A		intron	N/A	NP_036248.3
	CBLC	NM_001130852.1		c.1224+531G>A		intron	N/A	NP_001124324.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLC	ENST00000647358.2	MANE Select	c.1362+531G>A		intron	N/A	ENSP00000494162.1
	CBLC	ENST00000341505.4	TSL:1	c.1224+531G>A		intron	N/A	ENSP00000340250.4

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

African (AFR) AF: 0.289 AC: 11945 AN: 41306

American (AMR) AF: 0.0804 AC: 1223 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3470

East Asian (EAS) AF: 0.0921 AC: 471 AN: 5114

South Asian (SAS) AF: 0.115 AC: 554 AN: 4808

European-Finnish (FIN) AF: 0.123 AC: 1298 AN: 10518

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0725 AC: 4924 AN: 67916

Other (OTH) AF: 0.140 AC: 295 AN: 2110

Alfa AF: 0.0857 Hom.: 1714

Bravo AF: 0.142

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.0
DANN	Benign	0.83
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs10419669; hg19: chr19-45298069;