rs4864471

Positions:

• chr4-53560017-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LNX1	NM_001126328.3	c.380+13606C>A		intron_variant		ENST00000263925.8
LNX1	XM_005265785.6	c.380+13606C>A		intron_variant
LNX1	XM_024454262.2	c.380+13606C>A		intron_variant
LNX1	XM_047416328.1	c.380+13606C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX1	ENST00000263925.8	c.380+13606C>A		intron_variant		1	NM_001126328.3	P1

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

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0710

Gnomad4 EAS AF: 0.0584

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.0926

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.158

Alfa AF: 0.135 Hom.: 902

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4864471; hg19: chr4-54426184;