NM_001369817.2:c.-240-4615T>C

Variant names:

• chr1-89563632-T-C
• rs934475024
• NM_001369817.2:c.-240-4615T>C

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.-240-4615T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 hom., cov: 32)
• Consequence: LRRC8B NM_001369817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.603
• 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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC8B	NM_001369817.2	c.-240-4615T>C		intron_variant	Intron 1 of 5	ENST00000330947.7	NP_001356746.1
LRRC8B	NM_001134476.2	c.-240-4615T>C		intron_variant	Intron 3 of 7		NP_001127948.1
LRRC8B	NM_001369819.2	c.-240-4615T>C		intron_variant	Intron 2 of 6		NP_001356748.1
LRRC8B	NM_015350.4	c.-241+4596T>C		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.-240-4615T>C		intron_variant	Intron 1 of 5	5	NM_001369817.2	ENSP00000332674.2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.000479

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

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68020

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.89
PhyloP100		0.60

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: rs934475024; hg19: chr1-90029191;