rs10493831

Variant names:

• chr1-89725644-T-G
• rs10493831
• ENST00000370453.5:n.138+39033T>G

Variant summary

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

The ENST00000370453.5(ENSG00000271949):​n.138+39033T>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 151,968 control chromosomes in the GnomAD database, including 3,983 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 (3983 hom., cov: 32)
• Consequence: ENSG00000271949 ENST00000370453.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 1 publications found

Genes affected

ENSG00000271949 (HGNC:):

LRRC8C (HGNC:25075): (leucine rich repeat containing 8 VRAC subunit C) Enables volume-sensitive anion channel activity. Involved in cyclic-GMP-AMP transmembrane import across plasma membrane. Located in cytoplasm and plasma membrane. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC8C Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000271949	ENST00000370453.5	n.138+39033T>G		intron_variant	Intron 2 of 3	5		ENSP00000359482.5
LRRC8C	ENST00000479252.1	n.394-33213T>G		intron_variant	Intron 2 of 3	1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33482 AN: 151848 Hom.: 3983 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.235

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: 33491 AN: 151968 Hom.: 3983 Cov.: 32 AF XY: 0.222 AC XY: 16500 AN XY: 74294

African (AFR) AF: 0.145 AC: 6009 AN: 41430

American (AMR) AF: 0.301 AC: 4598 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3466

East Asian (EAS) AF: 0.318 AC: 1641 AN: 5162

South Asian (SAS) AF: 0.249 AC: 1198 AN: 4808

European-Finnish (FIN) AF: 0.263 AC: 2777 AN: 10542

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15952 AN: 67962

Other (OTH) AF: 0.221 AC: 466 AN: 2106

Alfa AF: 0.226 Hom.: 511

Bravo AF: 0.223

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.4
DANN	Benign	0.74
PhyloP100		-0.12

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: rs10493831; hg19: chr1-90191203;