rs6554112

Variant names:

• chr4-53552468-G-A
• rs6554112
• NM_001126328.3:c.380+21155C>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+21155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,062 control chromosomes in the GnomAD database, including 35,393 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 0.68 (35393 hom., cov: 32)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 4 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:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 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+21155C>T		intron	N/A	NP_001119800.1	Q8TBB1-1
	LNX1	NM_032622.3		c.92+5406C>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.380+21155C>T		intron	N/A	ENSP00000263925.7	Q8TBB1-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1017+126503G>A		intron	N/A	ENSP00000423325.1	A0A0B4J203
	LNX1	ENST00000306888.6	TSL:1	c.92+5406C>T		intron	N/A	ENSP00000302879.2	Q8TBB1-2

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103616 AN: 151944 Hom.: 35378 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.682 AC: 103669 AN: 152062 Hom.: 35393 Cov.: 32 AF XY: 0.680 AC XY: 50580 AN XY: 74328

African (AFR) AF: 0.653 AC: 27059 AN: 41442

American (AMR) AF: 0.655 AC: 10016 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2401 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3709 AN: 5174

South Asian (SAS) AF: 0.655 AC: 3154 AN: 4814

European-Finnish (FIN) AF: 0.668 AC: 7063 AN: 10576

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 47996 AN: 67978

Other (OTH) AF: 0.689 AC: 1456 AN: 2112

Alfa AF: 0.696 Hom.: 143047

Bravo AF: 0.678

Asia WGS AF: 0.653 AC: 2267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.43
DANN	Benign	0.38
PhyloP100		-0.027
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: rs6554112; hg19: chr4-54418635;