rs7660884

chr4-53560441-C-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+13182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,066 control chromosomes in the GnomAD database, including 3,489 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 (3489 hom., cov: 32)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNX1	NM_001126328.3	c.380+13182G>A		intron_variant		ENST00000263925.8
LNX1	XM_005265785.6	c.380+13182G>A		intron_variant
LNX1	XM_024454262.2	c.380+13182G>A		intron_variant
LNX1	XM_047416328.1	c.380+13182G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX1	ENST00000263925.8	c.380+13182G>A		intron_variant		1	NM_001126328.3	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27105 AN: 151948 Hom.: 3476 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0710

Gnomad EAS AF: 0.0578

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.142

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: 0.179 AC: 27160 AN: 152066 Hom.: 3489 Cov.: 32 AF XY: 0.173 AC XY: 12871 AN XY: 74350

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0710

Gnomad4 EAS AF: 0.0580

Gnomad4 SAS AF: 0.0437

Gnomad4 FIN AF: 0.0922

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.159

Alfa AF: 0.154 Hom.: 291

Bravo AF: 0.190

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.6
Dann	Benign	0.47

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: rs7660884; hg19: chr4-54426608;