rs1938032

Variant names:

• chr1-89892092-G-A
• rs1938032
• NM_001134479.2:c.-2-40975G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000337338.9(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 ENST00000337338.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.777
• Publications: 8 publications found

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]

ENSG00000271949 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000337338.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC8D	NM_001134479.2	MANE Select	c.-2-40975G>A		intron	N/A	NP_001127951.1
	LRRC8D	NM_018103.5		c.-2-40975G>A		intron	N/A	NP_060573.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC8D	ENST00000337338.9	TSL:2 MANE Select	c.-2-40975G>A		intron	N/A	ENSP00000338887.5
	LRRC8D	ENST00000394593.7	TSL:1	c.-2-40975G>A		intron	N/A	ENSP00000378093.3
	ENSG00000271949	ENST00000370453.5	TSL:5	n.*125-40975G>A		intron	N/A	ENSP00000359482.5

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

African (AFR) AF: 0.0776 AC: 3222 AN: 41518

American (AMR) AF: 0.119 AC: 1812 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 647 AN: 3472

East Asian (EAS) AF: 0.0237 AC: 123 AN: 5186

South Asian (SAS) AF: 0.135 AC: 652 AN: 4822

European-Finnish (FIN) AF: 0.138 AC: 1458 AN: 10584

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11880 AN: 67976

Other (OTH) AF: 0.128 AC: 270 AN: 2110

Alfa AF: 0.161 Hom.: 3593

Bravo AF: 0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.61
PhyloP100		0.78
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: rs1938032; hg19: chr1-90357651;