rs1215512

Variant names:

• chr1-89621952-C-A
• rs1215512
• XM_011542282.3:c.-5+5918C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-89621952-C-A
• chr1-89621952-C-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 (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-DT (HGNC:53731): (LRRC8C divergent transcript)

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443562.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC8C-DT	ENST00000443562.2	TSL:3	n.176+10064G>T		intron	N/A
	LRRC8C-DT	ENST00000655657.3		n.517+10064G>T		intron	N/A
	LRRC8C-DT	ENST00000660266.1		n.374-1165G>T		intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1215512;

hg19: chr1-90087511;