1-89583529-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001369817.2(LRRC8B):​c.879G>A​(p.Val293=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,612,836 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 112 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 110 hom. )

Consequence

LRRC8B
NM_001369817.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0630
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 -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 1-89583529-G-A is Benign according to our data. Variant chr1-89583529-G-A is described in ClinVar as [Benign]. Clinvar id is 780245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.063 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRC8BNM_001369817.2 linkuse as main transcriptc.879G>A p.Val293= synonymous_variant 5/6 ENST00000330947.7
LRRC8BNM_001134476.2 linkuse as main transcriptc.879G>A p.Val293= synonymous_variant 7/8
LRRC8BNM_001369819.2 linkuse as main transcriptc.879G>A p.Val293= synonymous_variant 6/7
LRRC8BNM_015350.4 linkuse as main transcriptc.879G>A p.Val293= synonymous_variant 8/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRC8BENST00000330947.7 linkuse as main transcriptc.879G>A p.Val293= synonymous_variant 5/65 NM_001369817.2 P1
LRRC8C-DTENST00000655657.3 linkuse as main transcriptn.701-105C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0215
AC:
3278
AN:
152142
Hom.:
111
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0749
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00897
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.0144
GnomAD3 exomes
AF:
0.00566
AC:
1415
AN:
250130
Hom.:
45
AF XY:
0.00404
AC XY:
546
AN XY:
135306
show subpopulations
Gnomad AFR exome
AF:
0.0784
Gnomad AMR exome
AF:
0.00304
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000159
Gnomad OTH exome
AF:
0.00246
GnomAD4 exome
AF:
0.00223
AC:
3255
AN:
1460576
Hom.:
110
Cov.:
34
AF XY:
0.00191
AC XY:
1386
AN XY:
726682
show subpopulations
Gnomad4 AFR exome
AF:
0.0805
Gnomad4 AMR exome
AF:
0.00329
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000927
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000980
Gnomad4 OTH exome
AF:
0.00469
GnomAD4 genome
AF:
0.0216
AC:
3282
AN:
152260
Hom.:
112
Cov.:
32
AF XY:
0.0205
AC XY:
1527
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0747
Gnomad4 AMR
AF:
0.00896
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.0142
Alfa
AF:
0.0132
Hom.:
49
Bravo
AF:
0.0244
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000415

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 testingInvitaeAug 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
1.7
DANN
Benign
0.84

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: rs35903285; hg19: chr1-90049088; API