4-53549271-C-T

Position:

• chr4-53549271-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.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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNX1	NM_001126328.3	c.380+24352G>A		intron_variant		ENST00000263925.8	NP_001119800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNX1	ENST00000263925.8	c.380+24352G>A		intron_variant		1	NM_001126328.3	ENSP00000263925.7
ENSG00000282278	ENST00000507166.5	c.1017+123306C>T		intron_variant		2		ENSP00000423325.1
LNX1	ENST00000306888.6	c.92+8603G>A		intron_variant		1		ENSP00000302879.2
LNX1-AS1	ENST00000511989.5	n.267-86C>T		intron_variant		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

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.267

Alfa AF: 0.148 Hom.: 293

Bravo AF: 0.252

Asia WGS AF: 0.239 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.40
DANN	Benign	0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs2280119; hg19: chr4-54415438;