1-89601247-G-A

Variant names:

• chr1-89601247-G-A
• rs1215494
• ENST00000443562.2:n.177-3043C>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.177-3043C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,034 control chromosomes in the GnomAD database, including 9,636 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 0.35 (9636 hom., cov: 32)
• Consequence: LRRC8C-DT ENST00000443562.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 2 publications found

Genes affected

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 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
LRRC8C-DT	ENST00000443562.2	n.177-3043C>T		intron_variant	Intron 1 of 4	3
LRRC8C-DT	ENST00000655657.3	n.518-13162C>T		intron_variant	Intron 2 of 3
LRRC8C-DT	ENST00000666228.2	n.451-13162C>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53913 AN: 151914 Hom.: 9625 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.355 AC: 53948 AN: 152034 Hom.: 9636 Cov.: 32 AF XY: 0.359 AC XY: 26697 AN XY: 74322

African (AFR) AF: 0.378 AC: 15689 AN: 41464

American (AMR) AF: 0.326 AC: 4977 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1202 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1154 AN: 5186

South Asian (SAS) AF: 0.341 AC: 1640 AN: 4806

European-Finnish (FIN) AF: 0.435 AC: 4583 AN: 10544

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23725 AN: 67970

Other (OTH) AF: 0.332 AC: 701 AN: 2112

Alfa AF: 0.344 Hom.: 16900

Bravo AF: 0.347

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.68
DANN	Benign	0.45
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs1215494; hg19: chr1-90066806;