chr1-89547674-A-G

Position:

• chr1-89547674-A-G

Variant summary

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

The NM_001369817.2(LRRC8B):​c.-240-20573A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,152 control chromosomes in the GnomAD database, including 4,041 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 0.22 (4041 hom., cov: 32)
• Consequence: LRRC8B NM_001369817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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]

LOC124904216 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC8B	NM_001369817.2	c.-240-20573A>G		intron_variant		ENST00000330947.7	NP_001356746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC8B	ENST00000330947.7	c.-240-20573A>G		intron_variant		5	NM_001369817.2	ENSP00000332674.2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33408 AN: 152034 Hom.: 4032 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.220 AC: 33444 AN: 152152 Hom.: 4041 Cov.: 32 AF XY: 0.218 AC XY: 16194 AN XY: 74388

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.0210

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.227

Alfa AF: 0.242 Hom.: 603

Bravo AF: 0.224

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.58
DANN	Benign	0.76

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: rs1077538; hg19: chr1-90013233; COSMIC: COSV58373759;