Variant chr9-128152283-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000277480.7(LCN2):c.576C>G(p.Ile192Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00068 in 1,613,018 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 1 hom. )

Consequence

LCN2
ENST00000277480.7 missense, splice_region

Scores

Splicing: ADA: 0.003748

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.73

Variant links:

Genes affected

LCN2 (HGNC:6526): (lipocalin 2) This gene encodes a protein that belongs to the lipocalin family. Members of this family transport small hydrophobic molecules such as lipids, steroid hormones and retinoids. The protein encoded by this gene is a neutrophil gelatinase-associated lipocalin and plays a role in innate immunity by limiting bacterial growth as a result of sequestering iron-containing siderophores. The presence of this protein in blood and urine is an early biomarker of acute kidney injury. This protein is thought to be be involved in multiple cellular processes, including maintenance of skin homeostasis, and suppression of invasiveness and metastasis. Mice lacking this gene are more susceptible to bacterial infection than wild type mice. [provided by RefSeq, Sep 2015]

LCN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04793048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCN2	NM_005564.5 linkuse as main transcript	c.576C>G	p.Ile192Met	missense_variant, splice_region_variant	5/7	ENST00000277480.7	NP_005555.2
LCN2	XM_047423376.1 linkuse as main transcript	c.576C>G	p.Ile192Met	missense_variant, splice_region_variant	5/6		XP_047279332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCN2	ENST00000277480.7 linkuse as main transcript	c.576C>G	p.Ile192Met	missense_variant, splice_region_variant	5/7	1	NM_005564.5	ENSP00000277480	P4	P80188-1

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000416

AC:

104

AN:

250158

Hom.:

AF XY:

0.000369

AC XY:

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000840

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000612

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000706

AC:

1032

AN:

1460800

Hom.:

Cov.:

AF XY:

0.000647

AC XY:

470

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000854

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000427

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.000563

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000338

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.576C>G (p.I192M) alteration is located in exon 5 (coding exon 5) of the LCN2 gene. This alteration results from a C to G substitution at nucleotide position 576, causing the isoleucine (I) at amino acid position 192 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.20

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.67

.;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

M;M;.

MutationTaster

Benign

0.96

N;N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.066

Sift

Benign

0.076

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.31

B;B;.

Vest4

0.26

MVP

0.092

MPC

0.057

ClinPred

0.013

GERP RS

-5.2

Varity_R

0.54

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0037

dbscSNV1_RF

Benign

0.35

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over