1-89621952-C-A

Variant names:

• chr1-89621952-C-A
• rs1215512
• ENST00000443562.2:n.176+10064G>T

Variant summary

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

The ENST00000443562.2(LRRC8C-DT):​n.176+10064G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,970 control chromosomes in the GnomAD database, including 21,999 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 0.52 (21999 hom., cov: 32)
• Consequence: LRRC8C-DT ENST00000443562.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• Publications: 6 publications found

Genes affected

LRRC8C-DT (HGNC:53731): (LRRC8C divergent transcript)

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC8C	XM_011542282.3	c.-5+5918C>A		intron_variant	Intron 1 of 2		XP_011540584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC8C-DT	ENST00000443562.2	n.176+10064G>T		intron_variant	Intron 1 of 4	3
LRRC8C-DT	ENST00000655657.3	n.517+10064G>T		intron_variant	Intron 2 of 3
LRRC8C-DT	ENST00000660266.1	n.374-1165G>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79400 AN: 151852 Hom.: 21961 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.523 AC: 79492 AN: 151970 Hom.: 21999 Cov.: 32 AF XY: 0.519 AC XY: 38564 AN XY: 74274

African (AFR) AF: 0.698 AC: 28928 AN: 41458

American (AMR) AF: 0.512 AC: 7825 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1544 AN: 3468

East Asian (EAS) AF: 0.736 AC: 3802 AN: 5164

South Asian (SAS) AF: 0.354 AC: 1704 AN: 4818

European-Finnish (FIN) AF: 0.379 AC: 3989 AN: 10530

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30246 AN: 67944

Other (OTH) AF: 0.504 AC: 1065 AN: 2112

Alfa AF: 0.484 Hom.: 31648

Bravo AF: 0.545

Asia WGS AF: 0.533 AC: 1855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.42
PhyloP100		0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1215512; hg19: chr1-90087511;