16-49280950-TAC-CAA

Variant names:

• chr16-49280950-TAC-CAA
• NM_004352.4:c.355_357delGTAinsTTG
• CBLN1 p.Val119Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004352.4(CBLN1):​c.355_357delGTAinsTTG​(p.Val119Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CBLN1 NM_004352.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.27
• Publications: 0 publications found

Genes affected

CBLN1 (HGNC:1543): (cerebellin 1 precursor) This gene encodes a cerebellum-specific precursor protein, precerebellin, with similarity to the globular (non-collagen-like) domain of complement component C1qB. Precerebellin is processed to give rise to several derivatives, including the hexadecapeptide, cerebellin, which is highly enriched in postsynaptic structures of Purkinje cells. Cerebellin has also been found in human and rat adrenals, where it has been shown to enhance the secretory activity of this gland. [provided by RefSeq, Aug 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004352.4. 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
	CBLN1	NM_004352.4	MANE Select	c.355_357delGTAinsTTG	p.Val119Leu	missense	N/A	NP_004343.1	P23435

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLN1	ENST00000219197.11	TSL:1 MANE Select	c.355_357delGTAinsTTG	p.Val119Leu	missense	N/A	ENSP00000219197.5	P23435
	CBLN1	ENST00000564786.1	TSL:2	n.*91_*93delGTAinsTTG		non_coding_transcript_exon	Exon 1 of 2	ENSP00000455718.1	H3BQD0
	CBLN1	ENST00000564786.1	TSL:2	n.*91_*93delGTAinsTTG		3_prime_UTR	Exon 1 of 2	ENSP00000455718.1	H3BQD0

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-49314861;