1-89646872-G-T

Variant names:

• chr1-89646872-G-T
• rs10754283
• NM_032270.5:c.-5+13550G>T

Variant summary

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

The NM_032270.5(LRRC8C):​c.-5+13550G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,806 control chromosomes in the GnomAD database, including 24,023 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 0.56 (24023 hom., cov: 32)
• Consequence: LRRC8C NM_032270.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• Publications: 8 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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000271949 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC8C	NM_032270.5	c.-5+13550G>T		intron_variant	Intron 1 of 2	ENST00000370454.9	NP_115646.3
LRRC8C	XM_011542282.3	c.-5+30838G>T		intron_variant	Intron 1 of 2		XP_011540584.1
LRRC8C	XM_047432040.1	c.-4+13550G>T		intron_variant	Intron 1 of 1		XP_047287996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC8C	ENST00000370454.9	c.-5+13550G>T		intron_variant	Intron 1 of 2	1	NM_032270.5	ENSP00000359483.4
ENSG00000271949	ENST00000370453.5	n.-5+13550G>T		intron_variant	Intron 1 of 3	5		ENSP00000359482.5

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84600 AN: 151688 Hom.: 23993 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.558 AC: 84669 AN: 151806 Hom.: 24023 Cov.: 32 AF XY: 0.559 AC XY: 41488 AN XY: 74186

African (AFR) AF: 0.546 AC: 22584 AN: 41398

American (AMR) AF: 0.669 AC: 10216 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1724 AN: 3464

East Asian (EAS) AF: 0.792 AC: 4096 AN: 5170

South Asian (SAS) AF: 0.436 AC: 2100 AN: 4816

European-Finnish (FIN) AF: 0.532 AC: 5596 AN: 10526

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36699 AN: 67852

Other (OTH) AF: 0.557 AC: 1174 AN: 2108

Alfa AF: 0.543 Hom.: 47210

Bravo AF: 0.574

Asia WGS AF: 0.584 AC: 2029 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.3
DANN	Benign	0.76
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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: rs10754283; hg19: chr1-90112431;