4-53464700-A-G

Variant names:

• chr4-53464700-A-G
• rs2412488
• NM_001126328.3:c.1893-3107T>C

Variant summary

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

The ENST00000263925.8(LNX1):​c.1893-3107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,980 control chromosomes in the GnomAD database, including 36,736 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 0.69 (36736 hom., cov: 32)
• Consequence: LNX1 ENST00000263925.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263925.8. 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.1893-3107T>C		intron	N/A	NP_001119800.1
	LNX1	NM_032622.3		c.1605-3107T>C		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.1893-3107T>C		intron	N/A	ENSP00000263925.7
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1017+38735A>G		intron	N/A	ENSP00000423325.1
	LNX1	ENST00000306888.6	TSL:1	c.1605-3107T>C		intron	N/A	ENSP00000302879.2

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105497 AN: 151862 Hom.: 36717 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.695 AC: 105567 AN: 151980 Hom.: 36736 Cov.: 32 AF XY: 0.696 AC XY: 51684 AN XY: 74292

African (AFR) AF: 0.672 AC: 27867 AN: 41474

American (AMR) AF: 0.701 AC: 10708 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2635 AN: 3472

East Asian (EAS) AF: 0.620 AC: 3203 AN: 5162

South Asian (SAS) AF: 0.712 AC: 3428 AN: 4814

European-Finnish (FIN) AF: 0.689 AC: 7296 AN: 10582

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48003 AN: 67884

Other (OTH) AF: 0.701 AC: 1480 AN: 2112

Alfa AF: 0.707 Hom.: 19235

Bravo AF: 0.694

Asia WGS AF: 0.682 AC: 2370 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.70
PhyloP100		-0.64
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: rs2412488; hg19: chr4-54330867;