Variant rs55689326 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_019594.4(LRRC8A):c.-2C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,604,536 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0080 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 19 hom. )

Consequence

LRRC8A
NM_019594.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.05

Variant links:

Genes affected

LRRC8A (HGNC:19027): (leucine rich repeat containing 8 VRAC subunit A) This gene encodes a protein belonging to the leucine-rich repeat family of proteins, which are involved in diverse biological processes, including cell adhesion, cellular trafficking, and hormone-receptor interactions. This family member is a putative four-pass transmembrane protein that plays a role in B cell development. Defects in this gene cause autosomal dominant non-Bruton type agammaglobulinemia, an immunodeficiency disease resulting from defects in B cell maturation. Multiple alternatively spliced transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

LRRC8A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 9-128907163-C-T is Benign according to our data. Variant chr9-128907163-C-T is described in ClinVar as [Benign]. Clinvar id is 2920758.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00795 (1212/152378) while in subpopulation AFR AF= 0.028 (1166/41598). AF 95% confidence interval is 0.0267. There are 14 homozygotes in gnomad4. There are 577 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1212 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC8A	NM_019594.4 link	c.-2C>T		5_prime_UTR_variant	Exon 3 of 4	ENST00000372600.9	NP_062540.2	Q8IWT6A0A024R892

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRRC8A	ENST00000372600 link	c.-2C>T	5_prime_UTR_variant	Exon 3 of 4	1	NM_019594.4	ENSP00000361682.4	Q8IWT6
LRRC8A	ENST00000372599 link	c.-2C>T	5_prime_UTR_variant	Exon 2 of 3	1		ENSP00000361680.3	Q8IWT6
LRRC8A	ENST00000259324 link	c.-2C>T	5_prime_UTR_variant	Exon 3 of 4	2		ENSP00000259324.5	Q8IWT6

Frequencies

GnomAD3 genomes

AF:

0.00790

AC:

1203

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0279

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00212

AC:

527

AN:

248472

Hom.:

AF XY:

0.00150

AC XY:

201

AN XY:

134292

show subpopulations

Gnomad AFR exome

AF:

0.0295

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000782

AC:

1135

AN:

1452158

Hom.:

Cov.:

AF XY:

0.000626

AC XY:

451

AN XY:

720480

show subpopulations

Gnomad4 AFR exome

AF:

0.0282

Gnomad4 AMR exome

AF:

0.00126

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000462

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.00795

AC:

1212

AN:

152378

Hom.:

Cov.:

AF XY:

0.00774

AC XY:

577

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.0280

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00332

Hom.:

Bravo

AF:

0.00954

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Agammaglobulinemia 5, autosomal dominant

Benign:1

Sep 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

LRRC8A-related disorder

Benign:1

Aug 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.94

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