rs1435218

Variant names:

• chr4-53535732-C-T
• rs1435218
• NM_001126328.3:c.381-27505G>A

Variant summary

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

The NM_001126328.3(LNX1):​c.381-27505G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 152,236 control chromosomes in the GnomAD database, including 583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association not found (★).

• Frequency: Genomes: 𝑓 0.089 (583 hom., cov: 32)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: association not found criteria provided, single submitter O:1
• Conservation: PhyloP100: -0.274
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0975 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.381-27505G>A		intron	N/A	NP_001119800.1	Q8TBB1-1
	LNX1	NM_032622.3		c.92+22142G>A		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.381-27505G>A		intron	N/A	ENSP00000263925.7	Q8TBB1-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1017+109767C>T		intron	N/A	ENSP00000423325.1	A0A0B4J203
	LNX1	ENST00000306888.6	TSL:1	c.92+22142G>A		intron	N/A	ENSP00000302879.2	Q8TBB1-2

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13507 AN: 152118 Hom.: 580 Cov.: 32

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.0895

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.0777

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.0986

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

GnomAD4 genome AF: 0.0888 AC: 13524 AN: 152236 Hom.: 583 Cov.: 32 AF XY: 0.0857 AC XY: 6380 AN XY: 74432

African (AFR) AF: 0.0873 AC: 3629 AN: 41556

American (AMR) AF: 0.0650 AC: 994 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3470

East Asian (EAS) AF: 0.0897 AC: 465 AN: 5186

South Asian (SAS) AF: 0.0673 AC: 324 AN: 4816

European-Finnish (FIN) AF: 0.0777 AC: 824 AN: 10600

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0995 AC: 6766 AN: 67994

Other (OTH) AF: 0.101 AC: 213 AN: 2112

Alfa AF: 0.0945 Hom.: 520

Bravo AF: 0.0883

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

ClinVar submissions

Significance: association not found

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	-	Lip and oral cavity carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.48
PhyloP100		-0.27
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: rs1435218; hg19: chr4-54401899;