rs1284772033

Variant names:

• chr19-7899122-G-C
• rs1284772033
• NM_025061.6:c.600G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-7899122-G-C
• chr19-7899122-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025061.6(LRRC8E):​c.600G>C​(p.Glu200Asp) 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. 15/21 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: 33)
• Consequence: LRRC8E NM_025061.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064427525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC8E	NM_025061.6	c.600G>C	p.Glu200Asp	missense_variant	Exon 3 of 3	ENST00000306708.11	NP_079337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC8E	ENST00000306708.11	c.600G>C	p.Glu200Asp	missense_variant	Exon 3 of 3	1	NM_025061.6	ENSP00000306524.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.6
DANN	Benign	0.61
DEOGEN2	Benign	0.0017	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.56	.;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.064	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.030	N;.;.
REVEL	Benign	0.051
Sift	Benign	0.55	T;.;.
Sift4G	Benign	0.61	T;T;T
Polyphen		0.76	P;P;.
Vest4		0.12
MutPred		0.14		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);.;
MVP		0.47
MPC		0.23
ClinPred		0.13	T
GERP RS		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Varity_R		0.044
gMVP		0.30

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: rs1284772033; hg19: chr19-7964007;