Variant 1-89584056-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001369817.2(LRRC8B):c.1406G>A(p.Arg469His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,614,088 control chromosomes in the GnomAD database, including 184 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.0047 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 166 hom. )

Consequence

LRRC8B
NM_001369817.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.33

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029286444).

BP6

Variant 1-89584056-G-A is Benign according to our data. Variant chr1-89584056-G-A is described in ClinVar as [Benign]. Clinvar id is 770489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LRRC8B	NM_001369817.2 linkuse as main transcript	c.1406G>A	p.Arg469His	missense_variant	5/6	ENST00000330947.7
LRRC8B	NM_001134476.2 linkuse as main transcript	c.1406G>A	p.Arg469His	missense_variant	7/8
LRRC8B	NM_001369819.2 linkuse as main transcript	c.1406G>A	p.Arg469His	missense_variant	6/7
LRRC8B	NM_015350.4 linkuse as main transcript	c.1406G>A	p.Arg469His	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC8B	ENST00000330947.7 linkuse as main transcript	c.1406G>A	p.Arg469His	missense_variant	5/6	5	NM_001369817.2	P1
LRRC8C-DT	ENST00000655657.3 linkuse as main transcript	n.701-632C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00467

AC:

711

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0259

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0506

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00938

AC:

2354

AN:

250828

Hom.:

AF XY:

0.00784

AC XY:

1063

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0363

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.0537

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00345

AC:

5042

AN:

1461812

Hom.:

166

Cov.:

AF XY:

0.00322

AC XY:

2342

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.0346

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.0764

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.00467

AC:

711

AN:

152276

Hom.:

Cov.:

AF XY:

0.00537

AC XY:

400

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.0259

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0509

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00306

Hom.:

Bravo

AF:

0.00719

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00825

AC:

1001

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.7

DANN

Benign

0.71

DEOGEN2

Benign

0.037

T;T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.68

.;.;.;T

MetaRNN

Benign

0.0029

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.1

N;N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

2.7

.;.;N;N

REVEL

Benign

0.019

Sift

Benign

1.0

.;.;T;T

Sift4G

Benign

0.65

.;.;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.074, 0.060

MVP

0.043

MPC

0.64

ClinPred

0.00058

GERP RS

-0.63

Varity_R

0.0087

gMVP

0.12

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