Variant 1-89583512-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBA1

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

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]

LRRC8B links:

LRRC8C-DT (HGNC:53731): (LRRC8C divergent transcript)

LRRC8C-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant where missense usually causes diseases, LRRC8B

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_single_submitter, 1 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
LRRC8B	NM_001369817.2 linkuse as main transcript	c.862G>A	p.Asp288Asn	missense_variant	5/6	ENST00000330947.7
LRRC8B	NM_001134476.2 linkuse as main transcript	c.862G>A	p.Asp288Asn	missense_variant	7/8
LRRC8B	NM_001369819.2 linkuse as main transcript	c.862G>A	p.Asp288Asn	missense_variant	6/7
LRRC8B	NM_015350.4 linkuse as main transcript	c.862G>A	p.Asp288Asn	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC8B	ENST00000330947.7 linkuse as main transcript	c.862G>A	p.Asp288Asn	missense_variant	5/6	5	NM_001369817.2	P1
LRRC8C-DT	ENST00000655657.3 linkuse as main transcript	n.701-88C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3268

AN:

152138

Hom.:

125

Cov.:

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.:

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.:

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.:

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.:

Bravo

AF:

0.0240

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0717

AC:

316

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00661

AC:

802

Asia WGS

AF:

0.00606

AC:

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 submitter

clinical testing

Invitae

Jan 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

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

MetaRNN

Benign

0.0035

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;M;M

MutationTaster

Benign

0.87

D;D;D

PrimateAI

Uncertain

0.62

Polyphen

0.95

P;P;P;P

Vest4

0.48, 0.47

MVP

0.17

MPC

1.4

ClinPred

0.029

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over