chr4-53548529-C-A

Variant names:

• chr4-53548529-C-A
• rs6820391
• NM_001126328.3:c.380+25094G>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.380+25094G>T 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 151,938 control chromosomes in the GnomAD database, including 5,021 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 (5021 hom., cov: 32)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 11 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=-0.86).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNX1	NM_001126328.3	MANE Select	c.380+25094G>T		intron	N/A	NP_001119800.1
	LNX1	NM_032622.3		c.92+9345G>T		intron	N/A	NP_116011.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNX1	ENST00000263925.8	TSL:1 MANE Select	c.380+25094G>T		intron	N/A	ENSP00000263925.7
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1017+122564C>A		intron	N/A	ENSP00000423325.1
	LNX1	ENST00000306888.6	TSL:1	c.92+9345G>T		intron	N/A	ENSP00000302879.2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38241 AN: 151818 Hom.: 5026 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.252 AC: 38254 AN: 151938 Hom.: 5021 Cov.: 32 AF XY: 0.252 AC XY: 18733 AN XY: 74248

African (AFR) AF: 0.173 AC: 7183 AN: 41438

American (AMR) AF: 0.295 AC: 4503 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 858 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1394 AN: 5164

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4810

European-Finnish (FIN) AF: 0.285 AC: 3011 AN: 10554

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19226 AN: 67948

Other (OTH) AF: 0.266 AC: 560 AN: 2106

Alfa AF: 0.277 Hom.: 18732

Bravo AF: 0.251

Asia WGS AF: 0.236 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.85
DANN	Benign	0.43
PhyloP100		-1.8
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: rs6820391; hg19: chr4-54414696;