chr4-53526948-A-G

Variant names:

• chr4-53526948-A-G
• rs17082951
• NM_001126328.3:c.381-18721T>C

Variant summary

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

The NM_001126328.3(LNX1):​c.381-18721T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,396 control chromosomes in the GnomAD database, including 5,470 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 (5470 hom., cov: 28)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 3 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 = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNX1	NM_001126328.3	c.381-18721T>C		intron_variant	Intron 2 of 10	ENST00000263925.8	NP_001119800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNX1	ENST00000263925.8	c.381-18721T>C		intron_variant	Intron 2 of 10	1	NM_001126328.3	ENSP00000263925.7
ENSG00000282278	ENST00000507166.5	c.1017+100983A>G		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40268 AN: 151276 Hom.: 5468 Cov.: 28

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.266 AC: 40298 AN: 151396 Hom.: 5470 Cov.: 28 AF XY: 0.263 AC XY: 19460 AN XY: 73928

African (AFR) AF: 0.199 AC: 8226 AN: 41296

American (AMR) AF: 0.326 AC: 4950 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3468

East Asian (EAS) AF: 0.333 AC: 1700 AN: 5104

South Asian (SAS) AF: 0.243 AC: 1157 AN: 4768

European-Finnish (FIN) AF: 0.251 AC: 2614 AN: 10424

Middle Eastern (MID) AF: 0.328 AC: 95 AN: 290

European-Non Finnish (NFE) AF: 0.292 AC: 19798 AN: 67832

Other (OTH) AF: 0.292 AC: 614 AN: 2102

Alfa AF: 0.283 Hom.: 12188

Bravo AF: 0.272

Asia WGS AF: 0.266 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		0.32
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: rs17082951; hg19: chr4-54393115;