1-89583512-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001369817.2(LRRC8B):​c.862G>A​(p.Asp288Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00397 in 1,613,332 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 125 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 107 hom. )

Consequence

LRRC8B
NM_001369817.2 missense

Scores

1
5
12

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.24
Variant links:
Genes affected
LRRC8B (HGNC:30692): (leucine rich repeat containing 8 VRAC subunit B) Contributes to volume-sensitive anion channel activity. Involved in anion transmembrane transport. Located in cytoplasm and plasma membrane. Is integral component of plasma membrane. Part of ion channel complex. [provided by Alliance of Genome Resources, Apr 2022]
LRRC8C-DT (HGNC:53731): (LRRC8C divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0035030544).
BP6
Variant 1-89583512-G-A is Benign according to our data. Variant chr1-89583512-G-A is described in ClinVar as [Benign]. Clinvar id is 782380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRC8BNM_001369817.2 linkuse as main transcriptc.862G>A p.Asp288Asn missense_variant 5/6 ENST00000330947.7
LRRC8BNM_001134476.2 linkuse as main transcriptc.862G>A p.Asp288Asn missense_variant 7/8
LRRC8BNM_001369819.2 linkuse as main transcriptc.862G>A p.Asp288Asn missense_variant 6/7
LRRC8BNM_015350.4 linkuse as main transcriptc.862G>A p.Asp288Asn missense_variant 8/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRC8BENST00000330947.7 linkuse as main transcriptc.862G>A p.Asp288Asn missense_variant 5/65 NM_001369817.2 P1
LRRC8C-DTENST00000655657.3 linkuse as main transcriptn.701-88C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0215
AC:
3268
AN:
152138
Hom.:
125
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0752
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00674
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.0144
GnomAD3 exomes
AF:
0.00537
AC:
1345
AN:
250366
Hom.:
46
AF XY:
0.00383
AC XY:
518
AN XY:
135360
show subpopulations
Gnomad AFR exome
AF:
0.0744
Gnomad AMR exome
AF:
0.00255
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000238
Gnomad OTH exome
AF:
0.00197
GnomAD4 exome
AF:
0.00214
AC:
3120
AN:
1461076
Hom.:
107
Cov.:
34
AF XY:
0.00180
AC XY:
1312
AN XY:
726908
show subpopulations
Gnomad4 AFR exome
AF:
0.0758
Gnomad4 AMR exome
AF:
0.00309
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000953
Gnomad4 OTH exome
AF:
0.00480
GnomAD4 genome
AF:
0.0215
AC:
3281
AN:
152256
Hom.:
125
Cov.:
32
AF XY:
0.0203
AC XY:
1509
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0753
Gnomad4 AMR
AF:
0.00667
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.0142
Alfa
AF:
0.00464
Hom.:
35
Bravo
AF:
0.0240
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.0717
AC:
316
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.00661
AC:
802
Asia WGS
AF:
0.00606
AC:
22
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 19, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.040
T;T;T;T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.84
.;.;.;T
MetaRNN
Benign
0.0035
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M;M;M;M
MutationTaster
Benign
0.87
D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.88
.;.;N;N
REVEL
Benign
0.15
Sift
Benign
0.49
.;.;T;T
Sift4G
Benign
0.50
.;.;T;T
Polyphen
0.95
P;P;P;P
Vest4
0.48, 0.47
MVP
0.17
MPC
1.4
ClinPred
0.029
T
GERP RS
5.3
Varity_R
0.21
gMVP
0.70

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17131746; hg19: chr1-90049071; API