rs6820391

Positions:

• chr4-53548529-C-A

Variant summary

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

The NM_001126328.3(LNX1):​c.380+25094G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,938 control chromosomes in the GnomAD database, including 5,021 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 0.25 (5021 hom., cov: 32)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNX1	NM_001126328.3	c.380+25094G>T		intron_variant		ENST00000263925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX1	ENST00000263925.8	c.380+25094G>T		intron_variant		1	NM_001126328.3	P1
LNX1	ENST00000306888.6	c.92+9345G>T		intron_variant		1
LNX1-AS1	ENST00000511989.5	n.267-828C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38241 AN: 151818 Hom.: 5026 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.252 AC: 38254 AN: 151938 Hom.: 5021 Cov.: 32 AF XY: 0.252 AC XY: 18733 AN XY: 74248

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.266

Alfa AF: 0.280 Hom.: 8289

Bravo AF: 0.251

Asia WGS AF: 0.236 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.85
DANN	Benign	0.43

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: rs6820391; hg19: chr4-54414696;