19-7899145-CG-AA

Variant names:

• chr19-7899145-CG-AA
• NM_025061.6:c.623_624delCGinsAA
• LRRC8E p.Ala208Glu

Variant summary

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

The NM_025061.6(LRRC8E):​c.623_624delCGinsAA​(p.Ala208Glu) variant causes a missense change involving the alteration of a non-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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A208V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC8E NM_025061.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 0 publications found

Genes affected

LRRC8E (HGNC:26272): (leucine rich repeat containing 8 VRAC subunit E) This gene encodes a member of a small, conserved family of proteins with similar structure, including a string of extracellular leucine-rich repeats. A related protein was shown to be involved in B-cell development. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

ENSG00000214248 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025061.6. 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
	LRRC8E	NM_025061.6	MANE Select	c.623_624delCGinsAA	p.Ala208Glu	missense	N/A	NP_079337.2
	LRRC8E	NM_001268284.3		c.623_624delCGinsAA	p.Ala208Glu	missense	N/A	NP_001255213.1	Q6NSJ5
	LRRC8E	NM_001268285.3		c.236_237delCGinsAA	p.Ala79Glu	missense	N/A	NP_001255214.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC8E	ENST00000306708.11	TSL:1 MANE Select	c.623_624delCGinsAA	p.Ala208Glu	missense	N/A	ENSP00000306524.5	Q6NSJ5
	LRRC8E	ENST00000618098.4	TSL:3	c.623_624delCGinsAA	p.Ala208Glu	missense	N/A	ENSP00000479953.1	Q6NSJ5
	LRRC8E	ENST00000907356.1		c.623_624delCGinsAA	p.Ala208Glu	missense	N/A	ENSP00000577415.1

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		0.18

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: chr19-7964030;