1-89730993-C-T

Position:

• chr1-89730993-C-T

Variant summary

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

The ENST00000479252.1(LRRC8C):​n.394-27864C>T variant causes a intron, non coding transcript 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: LRRC8C ENST00000479252.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC8C	ENST00000479252.1	n.394-27864C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.353

Alfa AF: 0.357 Hom.: 16558

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

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: rs2224652; hg19: chr1-90196552;