chr4-53464700-A-G

Position:

• chr4-53464700-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.1893-3107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,980 control chromosomes in the GnomAD database, including 36,736 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 0.69 (36736 hom., cov: 32)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNX1	NM_001126328.3	c.1893-3107T>C		intron_variant		ENST00000263925.8	NP_001119800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNX1	ENST00000263925.8	c.1893-3107T>C		intron_variant		1	NM_001126328.3	ENSP00000263925	P1
LNX1	ENST00000306888.6	c.1605-3107T>C		intron_variant		1		ENSP00000302879

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105497 AN: 151862 Hom.: 36717 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.695 AC: 105567 AN: 151980 Hom.: 36736 Cov.: 32 AF XY: 0.696 AC XY: 51684 AN XY: 74292

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.701

Alfa AF: 0.707 Hom.: 17291

Bravo AF: 0.694

Asia WGS AF: 0.682 AC: 2370 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.70

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: rs2412488; hg19: chr4-54330867;