20-31665976-CA-TG

Variant names:

• chr20-31665976-CA-TG
• NM_138578.3:c.674_675delTGinsCA
• BCL2L1 p.Leu225Pro

Variant summary

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

The NM_138578.3(BCL2L1):​c.674_675delTGinsCA​(p.Leu225Pro) variant causes a missense change. 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: 31)
• Consequence: BCL2L1 NM_138578.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.03
• Publications: 0 publications found

Genes affected

BCL2L1 (HGNC:992): (BCL2 like 1) The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The proteins encoded by this gene are located at the outer mitochondrial membrane, and have been shown to regulate outer mitochondrial membrane channel (VDAC) opening. VDAC regulates mitochondrial membrane potential, and thus controls the production of reactive oxygen species and release of cytochrome C by mitochondria, both of which are the potent inducers of cell apoptosis. Alternative splicing results in multiple transcript variants encoding two different isoforms. The longer isoform acts as an apoptotic inhibitor and the shorter isoform acts as an apoptotic activator. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138578.3. 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
	BCL2L1	NM_138578.3	MANE Select	c.674_675delTGinsCA	p.Leu225Pro	missense	N/A	NP_612815.1	Q07817-1
	BCL2L1	NM_001317919.2		c.674_675delTGinsCA	p.Leu225Pro	missense	N/A	NP_001304848.1	A0A0S2Z3C5
	BCL2L1	NM_001317920.2		c.674_675delTGinsCA	p.Leu225Pro	missense	N/A	NP_001304849.1	Q07817-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L1	ENST00000307677.5	TSL:1 MANE Select	c.674_675delTGinsCA	p.Leu225Pro	missense	N/A	ENSP00000302564.4	Q07817-1
	BCL2L1	ENST00000376062.6	TSL:1	c.674_675delTGinsCA	p.Leu225Pro	missense	N/A	ENSP00000365230.2	Q07817-1
	BCL2L1	ENST00000450273.2	TSL:3	c.896_897delTGinsCA	p.Leu299Pro	missense	N/A	ENSP00000406203.2	Q5TE64

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0

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: chr20-30253779;