NM_001369817.2:c.-240-11010A>G

Variant names:

• chr1-89557237-A-G
• rs922107
• NM_001369817.2:c.-240-11010A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369817.2(LRRC8B):​c.-240-11010A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,544 control chromosomes in the GnomAD database, including 20,009 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 0.51 (20009 hom., cov: 31)
• Consequence: LRRC8B NM_001369817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC8B	NM_001369817.2	c.-240-11010A>G		intron_variant	Intron 1 of 5	ENST00000330947.7	NP_001356746.1
LRRC8B	NM_001134476.2	c.-241+7266A>G		intron_variant	Intron 3 of 7		NP_001127948.1
LRRC8B	NM_001369819.2	c.-240-11010A>G		intron_variant	Intron 2 of 6		NP_001356748.1
LRRC8B	NM_015350.4	c.-566-1474A>G		intron_variant	Intron 3 of 8		NP_056165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC8B	ENST00000330947.7	c.-240-11010A>G		intron_variant	Intron 1 of 5	5	NM_001369817.2	ENSP00000332674.2

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77310 AN: 151428 Hom.: 19980 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.511 AC: 77394 AN: 151544 Hom.: 20009 Cov.: 31 AF XY: 0.510 AC XY: 37737 AN XY: 74022

African (AFR) AF: 0.473 AC: 19564 AN: 41324

American (AMR) AF: 0.519 AC: 7914 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1983 AN: 3462

East Asian (EAS) AF: 0.207 AC: 1069 AN: 5174

South Asian (SAS) AF: 0.576 AC: 2766 AN: 4802

European-Finnish (FIN) AF: 0.516 AC: 5401 AN: 10470

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.545 AC: 36937 AN: 67766

Other (OTH) AF: 0.523 AC: 1100 AN: 2104

Alfa AF: 0.529 Hom.: 85489

Bravo AF: 0.504

Asia WGS AF: 0.425 AC: 1480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.41
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs922107; hg19: chr1-90022796; COSMIC: COSV58373821;