chr1-89559960-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001369817.2(LRRC8B):​c.-240-8287C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: LRRC8B NM_001369817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC8B	NM_001369817.2	c.-240-8287C>G		intron_variant	Intron 1 of 5	ENST00000330947.7	NP_001356746.1
LRRC8B	NM_001134476.2	c.-240-8287C>G		intron_variant	Intron 3 of 7		NP_001127948.1
LRRC8B	NM_001369819.2	c.-240-8287C>G		intron_variant	Intron 2 of 6		NP_001356748.1
LRRC8B	NM_015350.4	c.-241+924C>G		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>G		intron_variant	Intron 1 of 5	5	NM_001369817.2	ENSP00000332674.2

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.1
DANN	Benign	0.68
PhyloP100		0.32

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;