rs1938032

Positions:

• chr1-89892092-G-A
• chr1-89892092-G-T

Variant summary

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

The NM_001134479.2(LRRC8D):​c.-2-40975G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,160 control chromosomes in the GnomAD database, including 1,509 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 0.13 (1509 hom., cov: 32)
• Consequence: LRRC8D NM_001134479.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.777

Genes affected

LRRC8D (HGNC:16992): (leucine rich repeat containing 8 VRAC subunit D) Enables volume-sensitive anion channel activity. Involved in cellular response to osmotic stress; organic acid transport; and protein hexamerization. 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC8D	NM_001134479.2	c.-2-40975G>A		intron_variant		ENST00000337338.9	NP_001127951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC8D	ENST00000337338.9	c.-2-40975G>A		intron_variant		2	NM_001134479.2	ENSP00000338887	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20283 AN: 152042 Hom.: 1509 Cov.: 32

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.133 AC: 20284 AN: 152160 Hom.: 1509 Cov.: 32 AF XY: 0.131 AC XY: 9766 AN XY: 74396

Gnomad4 AFR AF: 0.0776

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0237

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.128

Alfa AF: 0.165 Hom.: 2943

Bravo AF: 0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.61

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: rs1938032; hg19: chr1-90357651;