1-89730993-C-T

Variant names:

• chr1-89730993-C-T
• rs2224652
• ENST00000370453.5:n.138+44382C>T

Variant summary

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

The ENST00000370453.5(ENSG00000271949):​n.138+44382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,040 control chromosomes in the GnomAD database, including 9,882 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 0.36 (9882 hom., cov: 32)
• Consequence: ENSG00000271949 ENST00000370453.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28
• Publications: 5 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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 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+44382C>T		intron_variant	Intron 2 of 3	5		ENSP00000359482.5
LRRC8C	ENST00000479252.1	n.394-27864C>T		intron_variant	Intron 2 of 3	1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54513 AN: 151922 Hom.: 9867 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.359 AC: 54559 AN: 152040 Hom.: 9882 Cov.: 32 AF XY: 0.360 AC XY: 26749 AN XY: 74290

African (AFR) AF: 0.344 AC: 14270 AN: 41472

American (AMR) AF: 0.392 AC: 5982 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1385 AN: 3468

East Asian (EAS) AF: 0.505 AC: 2614 AN: 5174

South Asian (SAS) AF: 0.313 AC: 1510 AN: 4820

European-Finnish (FIN) AF: 0.347 AC: 3664 AN: 10544

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24095 AN: 67970

Other (OTH) AF: 0.353 AC: 745 AN: 2108

Alfa AF: 0.356 Hom.: 26520

Bravo AF: 0.361

Asia WGS AF: 0.379 AC: 1319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.23
DANN	Benign	0.57
PhyloP100		-3.3

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: rs2224652; hg19: chr1-90196552;