rs9512755

Variant names:

• chr13-27584092-C-T
• rs9512755
• NM_153371.4:c.-100-2289G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153371.4(LNX2):​c.-100-2289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 152,178 control chromosomes in the GnomAD database, including 1,024 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 0.098 (1024 hom., cov: 31)
• Consequence: LNX2 NM_153371.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 8 publications found

Genes affected

LNX2 (HGNC:20421): (ligand of numb-protein X 2) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNX2	NM_153371.4	c.-100-2289G>A		intron_variant	Intron 1 of 9	ENST00000316334.5	NP_699202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNX2	ENST00000316334.5	c.-100-2289G>A		intron_variant	Intron 1 of 9	1	NM_153371.4	ENSP00000325929.3
LNX2	ENST00000649248.1	c.-100-2289G>A		intron_variant	Intron 2 of 10			ENSP00000497224.1

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14844 AN: 152060 Hom.: 1024 Cov.: 31

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.0998

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

GnomAD4 genome AF: 0.0975 AC: 14841 AN: 152178 Hom.: 1024 Cov.: 31 AF XY: 0.100 AC XY: 7447 AN XY: 74406

African (AFR) AF: 0.0223 AC: 926 AN: 41530

American (AMR) AF: 0.0808 AC: 1236 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3470

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5182

South Asian (SAS) AF: 0.0901 AC: 434 AN: 4818

European-Finnish (FIN) AF: 0.190 AC: 2007 AN: 10586

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9498 AN: 67982

Other (OTH) AF: 0.0988 AC: 208 AN: 2106

Alfa AF: 0.123 Hom.: 2120

Bravo AF: 0.0845

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.46
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9512755; hg19: chr13-28158229;