chr9-128151891-C-G

Variant names:

• chr9-128151891-C-G
• rs11794980
• NM_005564.5:c.356-15C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.57
• Publications: 13 publications found

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]

ENSG00000308297 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005564.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN2	NM_005564.5	MANE Select	c.356-15C>G		intron	N/A	NP_005555.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN2	ENST00000277480.7	TSL:1 MANE Select	c.356-15C>G		intron	N/A	ENSP00000277480.2
	LCN2	ENST00000372998.1	TSL:5	c.362-15C>G		intron	N/A	ENSP00000362089.1
	LCN2	ENST00000373017.5	TSL:5	c.356-15C>G		intron	N/A	ENSP00000362108.1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75282 AN: 152008 Hom.: 21700 Cov.: 33

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

GnomAD2 exomes AF: 0.592 AC: 148474 AN: 250978 AF XY: 0.598

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 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.: 56 AF XY: 0.615 AC XY: 447349 AN XY: 726918

African (AFR) AF: 0.155 AC: 5203 AN: 33478

American (AMR) AF: 0.727 AC: 32489 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 15003 AN: 26104

East Asian (EAS) AF: 0.492 AC: 19541 AN: 39698

South Asian (SAS) AF: 0.642 AC: 55380 AN: 86224

European-Finnish (FIN) AF: 0.559 AC: 29857 AN: 53372

Middle Eastern (MID) AF: 0.550 AC: 3145 AN: 5716

European-Non Finnish (NFE) AF: 0.631 AC: 701185 AN: 1111592

Other (OTH) AF: 0.590 AC: 35600 AN: 60366

GnomAD4 genome AF: 0.495 AC: 75318 AN: 152126 Hom.: 21721 Cov.: 33 AF XY: 0.497 AC XY: 36992 AN XY: 74372

African (AFR) AF: 0.176 AC: 7326 AN: 41534

American (AMR) AF: 0.666 AC: 10195 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2036 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2392 AN: 5144

South Asian (SAS) AF: 0.639 AC: 3079 AN: 4822

European-Finnish (FIN) AF: 0.559 AC: 5920 AN: 10592

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42438 AN: 67948

Other (OTH) AF: 0.527 AC: 1111 AN: 2110

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.027
DANN	Benign	0.32
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11794980; hg19: chr9-130914170; COSMIC: COSV52980605; COSMIC: COSV52980605;