4-53579548-C-T

Variant names:

• chr4-53579548-C-T
• rs6826933
• NM_001126328.3:c.-86-5460G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ENSG00000282278 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126328.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNX1	NM_001126328.3	MANE Select	c.-86-5460G>A		intron	N/A	NP_001119800.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNX1	ENST00000263925.8	TSL:1 MANE Select	c.-86-5460G>A		intron	N/A	ENSP00000263925.7
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1017+153583C>T		intron	N/A	ENSP00000423325.1
	LNX1	ENST00000513421.5	TSL:5	c.-86-5460G>A		intron	N/A	ENSP00000426445.1

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

African (AFR) AF: 0.312 AC: 12903 AN: 41414

American (AMR) AF: 0.314 AC: 4779 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1221 AN: 5172

South Asian (SAS) AF: 0.199 AC: 957 AN: 4802

European-Finnish (FIN) AF: 0.271 AC: 2854 AN: 10542

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16553 AN: 67956

Other (OTH) AF: 0.266 AC: 559 AN: 2104

Alfa AF: 0.252 Hom.: 2776

Bravo AF: 0.276

Asia WGS AF: 0.221 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.79
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6826933; hg19: chr4-54445715;