rs922106

Variant names:

• chr1-89559960-C-A
• rs922106
• NM_001369817.2:c.-240-8287C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-89559960-C-A
• chr1-89559960-C-G
• chr1-89559960-C-T

Variant summary

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

The NM_001369817.2(LRRC8B):​c.-240-8287C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,970 control chromosomes in the GnomAD database, including 13,461 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 0.40 (13461 hom., cov: 30)
• Consequence: LRRC8B NM_001369817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 16 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC8B	NM_001369817.2	c.-240-8287C>A		intron_variant	Intron 1 of 5	ENST00000330947.7	NP_001356746.1
LRRC8B	NM_001134476.2	c.-240-8287C>A		intron_variant	Intron 3 of 7		NP_001127948.1
LRRC8B	NM_001369819.2	c.-240-8287C>A		intron_variant	Intron 2 of 6		NP_001356748.1
LRRC8B	NM_015350.4	c.-241+924C>A		intron_variant	Intron 4 of 8		NP_056165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC8B	ENST00000330947.7	c.-240-8287C>A		intron_variant	Intron 1 of 5	5	NM_001369817.2	ENSP00000332674.2

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60320 AN: 151852 Hom.: 13457 Cov.: 30

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.397 AC: 60349 AN: 151970 Hom.: 13461 Cov.: 30 AF XY: 0.399 AC XY: 29624 AN XY: 74270

African (AFR) AF: 0.190 AC: 7876 AN: 41466

American (AMR) AF: 0.444 AC: 6785 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1809 AN: 3472

East Asian (EAS) AF: 0.201 AC: 1036 AN: 5160

South Asian (SAS) AF: 0.551 AC: 2646 AN: 4804

European-Finnish (FIN) AF: 0.477 AC: 5030 AN: 10542

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.496 AC: 33706 AN: 67936

Other (OTH) AF: 0.415 AC: 875 AN: 2110

Alfa AF: 0.473 Hom.: 45695

Bravo AF: 0.381

Asia WGS AF: 0.347 AC: 1210 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.68
PhyloP100		0.32
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: rs922106; hg19: chr1-90025519;