rs10493825

Positions:

• chr1-89551696-G-A
• chr1-89551696-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369817.2(LRRC8B):​c.-240-16551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,128 control chromosomes in the GnomAD database, including 3,502 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3502 hom., cov: 32)
• Consequence: LRRC8B NM_001369817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC8B	NM_001369817.2	c.-240-16551G>A		intron_variant		ENST00000330947.7
LRRC8B	NM_001134476.2	c.-241+1725G>A		intron_variant
LRRC8B	NM_001369819.2	c.-240-16551G>A		intron_variant
LRRC8B	NM_015350.4	c.-567+1725G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC8B	ENST00000330947.7	c.-240-16551G>A		intron_variant		5	NM_001369817.2	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29165 AN: 152010 Hom.: 3495 Cov.: 32

Gnomad AFR AF: 0.0674

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.203

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.192 AC: 29177 AN: 152128 Hom.: 3502 Cov.: 32 AF XY: 0.191 AC XY: 14176 AN XY: 74372

Gnomad4 AFR AF: 0.0673

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.201

Alfa AF: 0.236 Hom.: 5786

Bravo AF: 0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs10493825; hg19: chr1-90017255;