chr4-53560017-G-T

Variant names:

• chr4-53560017-G-T
• rs4864471
• NM_001126328.3:c.380+13606C>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.380+13606C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,940 control chromosomes in the GnomAD database, including 3,472 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 0.18 (3472 hom., cov: 31)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNX1	NM_001126328.3	c.380+13606C>A		intron_variant	Intron 2 of 10	ENST00000263925.8	NP_001119800.1
LNX1	XM_005265785.6	c.380+13606C>A		intron_variant	Intron 2 of 10		XP_005265842.1
LNX1	XM_024454262.2	c.380+13606C>A		intron_variant	Intron 3 of 11		XP_024310030.1
LNX1	XM_047416328.1	c.380+13606C>A		intron_variant	Intron 2 of 9		XP_047272284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNX1	ENST00000263925.8	c.380+13606C>A		intron_variant	Intron 2 of 10	1	NM_001126328.3	ENSP00000263925.7
ENSG00000282278	ENST00000507166.5	c.1017+134052G>T		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27059 AN: 151822 Hom.: 3458 Cov.: 31

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0710

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.0926

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.178 AC: 27115 AN: 151940 Hom.: 3472 Cov.: 31 AF XY: 0.173 AC XY: 12851 AN XY: 74286

African (AFR) AF: 0.364 AC: 15073 AN: 41404

American (AMR) AF: 0.112 AC: 1715 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0710 AC: 246 AN: 3464

East Asian (EAS) AF: 0.0584 AC: 302 AN: 5168

South Asian (SAS) AF: 0.0439 AC: 212 AN: 4826

European-Finnish (FIN) AF: 0.0926 AC: 979 AN: 10578

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.119 AC: 8083 AN: 67930

Other (OTH) AF: 0.158 AC: 334 AN: 2108

Alfa AF: 0.138 Hom.: 1381

Bravo AF: 0.190

Asia WGS AF: 0.0940 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.38
PhyloP100		-2.1
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: rs4864471; hg19: chr4-54426184;