rs755970278

Variant names:

• chr19-7895624-C-A
• rs755970278
• NM_025061.6:c.21C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-7895624-C-A
• chr19-7895624-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025061.6(LRRC8E):​c.21C>A​(p.Phe7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC8E NM_025061.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24375823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC8E	NM_025061.6	c.21C>A	p.Phe7Leu	missense_variant	Exon 2 of 3	ENST00000306708.11	NP_079337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC8E	ENST00000306708.11	c.21C>A	p.Phe7Leu	missense_variant	Exon 2 of 3	1	NM_025061.6	ENSP00000306524.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00062	T;T;.;T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.87	.;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L;L;.;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.35	N;.;.;.;.
REVEL	Benign	0.24
Sift	Benign	1.0	T;.;.;.;.
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		1.0	D;D;.;.;.
Vest4		0.53
MutPred		0.23		Loss of ubiquitination at K8 (P = 0.1037);Loss of ubiquitination at K8 (P = 0.1037);Loss of ubiquitination at K8 (P = 0.1037);Loss of ubiquitination at K8 (P = 0.1037);Loss of ubiquitination at K8 (P = 0.1037);
MVP		0.65
MPC		0.98
ClinPred		0.73	D
GERP RS		4.7
Varity_R		0.23
gMVP		0.63

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: rs755970278; hg19: chr19-7960509;