rs6554112

Positions:

• chr4-53552468-G-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+21155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,062 control chromosomes in the GnomAD database, including 35,393 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 0.68 (35393 hom., cov: 32)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNX1	NM_001126328.3	c.380+21155C>T		intron_variant		ENST00000263925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX1	ENST00000263925.8	c.380+21155C>T		intron_variant		1	NM_001126328.3	P1
LNX1	ENST00000306888.6	c.92+5406C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103616 AN: 151944 Hom.: 35378 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.682 AC: 103669 AN: 152062 Hom.: 35393 Cov.: 32 AF XY: 0.680 AC XY: 50580 AN XY: 74328

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.689

Alfa AF: 0.700 Hom.: 63010

Bravo AF: 0.678

Asia WGS AF: 0.653 AC: 2267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.43
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: rs6554112; hg19: chr4-54418635;