4-53535732-C-T

Position:

• chr4-53535732-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.381-27505G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 152,236 control chromosomes in the GnomAD database, including 583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association not found (★).

• Frequency: Genomes: 𝑓 0.089 (583 hom., cov: 32)
• Consequence: LNX1 NM_001126328.3 intron
• Clinical Significance: association not found criteria provided, single submitter O:1
• Conservation: PhyloP100: -0.274

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LNX1	NM_001126328.3	c.381-27505G>A		intron_variant		ENST00000263925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LNX1	ENST00000263925.8	c.381-27505G>A		intron_variant		1	NM_001126328.3	P1
LNX1	ENST00000306888.6	c.92+22142G>A		intron_variant		1
LNX1-AS1	ENST00000511989.5	n.266+11385C>T		intron_variant, non_coding_transcript_variant		2
LNX1-AS1	ENST00000514364.1	n.240-3361C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13507 AN: 152118 Hom.: 580 Cov.: 32

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.0895

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.0777

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.0986

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

GnomAD4 genome AF: 0.0888 AC: 13524 AN: 152236 Hom.: 583 Cov.: 32 AF XY: 0.0857 AC XY: 6380 AN XY: 74432

Gnomad4 AFR AF: 0.0873

Gnomad4 AMR AF: 0.0650

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.0897

Gnomad4 SAS AF: 0.0673

Gnomad4 FIN AF: 0.0777

Gnomad4 NFE AF: 0.0995

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0934 Hom.: 361

Bravo AF: 0.0883

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Significance: association not found

Submissions summary: Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lip and oral cavity carcinoma Other:1

association not found, criteria provided, single submitter

case-control

Department of Biological Science, Sunandan Divatia School of Science, NMIMS University

Nov 02, 2015

No significant association was observed between SNP rs1435218 with oral cancer. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.48

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: rs1435218; hg19: chr4-54401899;