4-53526948-A-G

Position:

• chr4-53526948-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001126328.3(LNX1):​c.381-18721T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,396 control chromosomes in the GnomAD database, including 5,470 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 0.27 (5470 hom., cov: 28)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

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]

LNX1-AS1 (HGNC:40345): (LNX1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNX1	NM_001126328.3	c.381-18721T>C		intron_variant		ENST00000263925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX1	ENST00000263925.8	c.381-18721T>C		intron_variant		1	NM_001126328.3	P1
LNX1	ENST00000306888.6	c.93-18721T>C		intron_variant		1
LNX1-AS1	ENST00000511989.5	n.266+2601A>G		intron_variant, non_coding_transcript_variant		2
LNX1-AS1	ENST00000514364.1	n.239+2601A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40268 AN: 151276 Hom.: 5468 Cov.: 28

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.266 AC: 40298 AN: 151396 Hom.: 5470 Cov.: 28 AF XY: 0.263 AC XY: 19460 AN XY: 73928

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.292

Alfa AF: 0.290 Hom.: 8743

Bravo AF: 0.272

Asia WGS AF: 0.266 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.74

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: rs17082951; hg19: chr4-54393115;