rs10754283

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-89646872-G-A
• chr1-89646872-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032270.5(LRRC8C):​c.-5+13550G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,774 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC8C	NM_032270.5	c.-5+13550G>A		intron_variant	Intron 1 of 2	ENST00000370454.9	NP_115646.3
LRRC8C	XM_011542282.3	c.-5+30838G>A		intron_variant	Intron 1 of 2		XP_011540584.1
LRRC8C	XM_047432040.1	c.-4+13550G>A		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>A		intron_variant	Intron 1 of 2	1	NM_032270.5	ENSP00000359483.4
ENSG00000271949	ENST00000370453.5	n.-5+13550G>A		intron_variant	Intron 1 of 3	5		ENSP00000359482.5

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151774 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151774 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000242 AC: 1 AN: 41300

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67890

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 47210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.4
DANN	Benign	0.95
PhyloP100		0.46

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;