chr9-128149536-G-C

Variant names:

• chr9-128149536-G-C
• NM_005564.5:c.11G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005564.5(LCN2):​c.11G>C​(p.Gly4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LCN2 NM_005564.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545

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]

ACMG classification

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=0.058465302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCN2	NM_005564.5	c.11G>C	p.Gly4Ala	missense_variant	Exon 1 of 7	ENST00000277480.7	NP_005555.2
LCN2	XM_047423376.1	c.11G>C	p.Gly4Ala	missense_variant	Exon 1 of 6		XP_047279332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCN2	ENST00000277480.7	c.11G>C	p.Gly4Ala	missense_variant	Exon 1 of 7	1	NM_005564.5	ENSP00000277480.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1459918 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.4
DANN	Benign	0.76
DEOGEN2	Benign	0.24	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.38	.;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M;.
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Benign	0.025
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.043	B;B;.
Vest4		0.11
MutPred		0.39		Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);
MVP		0.15
MPC		0.026
ClinPred		0.098	T
GERP RS		0.55
Varity_R		0.081
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130911815;