4-53524984-C-A

Variant names:

• chr4-53524984-C-A
• rs6831173
• NM_001126328.3:c.381-16757G>T

Variant summary

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

The NM_001126328.3(LNX1):​c.381-16757G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,026 control chromosomes in the GnomAD database, including 1,450 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 0.13 (1450 hom., cov: 32)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 2 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:):

LNX1-AS1 (HGNC:40345): (LNX1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNX1	NM_001126328.3	MANE Select	c.381-16757G>T		intron	N/A	NP_001119800.1	Q8TBB1-1
	LNX1	NM_032622.3		c.93-16757G>T		intron	N/A	NP_116011.2	Q8TBB1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNX1	ENST00000263925.8	TSL:1 MANE Select	c.381-16757G>T		intron	N/A	ENSP00000263925.7	Q8TBB1-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1017+99019C>A		intron	N/A	ENSP00000423325.1	A0A0B4J203
	LNX1	ENST00000306888.6	TSL:1	c.93-16757G>T		intron	N/A	ENSP00000302879.2	Q8TBB1-2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19632 AN: 151908 Hom.: 1446 Cov.: 32

Gnomad AFR AF: 0.0795

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.129 AC: 19630 AN: 152026 Hom.: 1450 Cov.: 32 AF XY: 0.130 AC XY: 9640 AN XY: 74316

African (AFR) AF: 0.0793 AC: 3287 AN: 41464

American (AMR) AF: 0.118 AC: 1807 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 789 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1379 AN: 5166

South Asian (SAS) AF: 0.155 AC: 746 AN: 4814

European-Finnish (FIN) AF: 0.0789 AC: 835 AN: 10578

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10183 AN: 67948

Other (OTH) AF: 0.163 AC: 342 AN: 2102

Alfa AF: 0.128 Hom.: 816

Bravo AF: 0.130

Asia WGS AF: 0.215 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.038
DANN	Benign	0.23
PhyloP100		-1.1
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: rs6831173; hg19: chr4-54391151;