4-53549271-C-T

Variant names:

• chr4-53549271-C-T
• rs2280119
• NM_001126328.3:c.380+24352G>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.380+24352G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,982 control chromosomes in the GnomAD database, including 5,034 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 0.25 (5034 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 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.380+24352G>A		intron	N/A	NP_001119800.1	Q8TBB1-1
	LNX1	NM_032622.3		c.92+8603G>A		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.380+24352G>A		intron	N/A	ENSP00000263925.7	Q8TBB1-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1017+123306C>T		intron	N/A	ENSP00000423325.1	A0A0B4J203
	LNX1	ENST00000306888.6	TSL:1	c.92+8603G>A		intron	N/A	ENSP00000302879.2	Q8TBB1-2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38328 AN: 151864 Hom.: 5039 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.252 AC: 38342 AN: 151982 Hom.: 5034 Cov.: 31 AF XY: 0.253 AC XY: 18775 AN XY: 74284

African (AFR) AF: 0.174 AC: 7215 AN: 41474

American (AMR) AF: 0.295 AC: 4507 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1397 AN: 5172

South Asian (SAS) AF: 0.229 AC: 1103 AN: 4820

European-Finnish (FIN) AF: 0.285 AC: 2998 AN: 10514

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19251 AN: 67948

Other (OTH) AF: 0.267 AC: 564 AN: 2110

Alfa AF: 0.150 Hom.: 305

Bravo AF: 0.252

Asia WGS AF: 0.239 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.40
DANN	Benign	0.28
PhyloP100		-0.76
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: rs2280119; hg19: chr4-54415438;