Genetic Variant LCN2:c.356-15C>G (chr9-128151891-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005564.5(LCN2):c.356-15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,613,372 control chromosomes in the GnomAD database, including 302,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 21721 hom., cov: 33)

Exomes 𝑓: 0.61 ( 280840 hom. )

Consequence

LCN2
NM_005564.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.57

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 9-128151891-C-G is Benign according to our data. Variant chr9-128151891-C-G is described in ClinVar as [Benign]. Clinvar id is 403029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCN2	NM_005564.5 link	c.356-15C>G		intron_variant	Intron 3 of 6	ENST00000277480.7	NP_005555.2	P80188-1
LCN2	XM_047423376.1 link	c.356-15C>G		intron_variant	Intron 3 of 5		XP_047279332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCN2	ENST00000277480.7 link	c.356-15C>G		intron_variant	Intron 3 of 6	1	NM_005564.5	ENSP00000277480.2		P80188-1

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75282

AN:

152008

Hom.:

21700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.729

Gnomad AMR

AF:

0.666

Gnomad ASJ

AF:

0.586

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.559

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.625

Gnomad OTH

AF:

0.523

GnomAD3 exomes

AF:

0.592

AC:

148474

AN:

250978

Hom.:

46166

AF XY:

0.598

AC XY:

81080

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.735

Gnomad ASJ exome

AF:

0.578

Gnomad EAS exome

AF:

0.487

Gnomad SAS exome

AF:

0.640

Gnomad FIN exome

AF:

0.553

Gnomad NFE exome

AF:

0.621

Gnomad OTH exome

AF:

0.595

GnomAD4 exome

AF:

0.614

AC:

897403

AN:

1461246

Hom.:

280840

Cov.:

AF XY:

0.615

AC XY:

447349

AN XY:

726918

show subpopulations

Gnomad4 AFR exome

AF:

0.155

Gnomad4 AMR exome

AF:

0.727

Gnomad4 ASJ exome

AF:

0.575

Gnomad4 EAS exome

AF:

0.492

Gnomad4 SAS exome

AF:

0.642

Gnomad4 FIN exome

AF:

0.559

Gnomad4 NFE exome

AF:

0.631

Gnomad4 OTH exome

AF:

0.590

GnomAD4 genome

AF:

0.495

AC:

75318

AN:

152126

Hom.:

21721

Cov.:

AF XY:

0.497

AC XY:

36992

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.666

Gnomad4 ASJ

AF:

0.586

Gnomad4 EAS

AF:

0.465

Gnomad4 SAS

AF:

0.639

Gnomad4 FIN

AF:

0.559

Gnomad4 NFE

AF:

0.625

Gnomad4 OTH

AF:

0.527

Alfa

AF:

0.495

Hom.:

2908

Bravo

AF:

0.488

Asia WGS

AF:

0.529

AC:

1839

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.027

DANN

Benign

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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