rs6826933

chr4-53579548-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001126328.3(LNX1):c.-86-5460G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,908 control chromosomes in the GnomAD database, including 5,630 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 0.27 (5630 hom., cov: 32)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

Genes affected

LNX1 (HGNC:6657): (ligand of numb-protein X 1) This gene encodes a membrane-bound protein that is involved in signal transduction and protein interactions. The encoded product is an E3 ubiquitin-protein ligase, which mediates ubiquitination and subsequent proteasomal degradation of proteins containing phosphotyrosine binding (PTB) domains. This protein may play an important role in tumorogenesis. Alternatively spliced transcript variants encoding distinct isoforms have been described. A pseudogene, which is located on chromosome 17, has been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNX1	NM_001126328.3	c.-86-5460G>A		intron_variant		ENST00000263925.8
LNX1	XM_005265785.6	c.-86-5460G>A		intron_variant
LNX1	XM_024454262.2	c.-171-209G>A		intron_variant
LNX1	XM_047416328.1	c.-86-5460G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX1	ENST00000263925.8	c.-86-5460G>A		intron_variant		1	NM_001126328.3	P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40905 AN: 151790 Hom.: 5620 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.270 AC: 40943 AN: 151908 Hom.: 5630 Cov.: 32 AF XY: 0.271 AC XY: 20111 AN XY: 74254

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.266

Alfa AF: 0.252 Hom.: 2527

Bravo AF: 0.276

Asia WGS AF: 0.221 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.9
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6826933; hg19: chr4-54445715;