9-128151921-C-T

Position:

• chr9-128151921-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000277480.7(LCN2):​c.371C>T​(p.Thr124Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,614,110 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (15 hom., cov: 33)
  • Exomes 𝑓: 0.00076 (17 hom.)
• Consequence: LCN2 ENST00000277480.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.154

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033982694).
• BP6: Variant 9-128151921-C-T is Benign according to our data. Variant chr9-128151921-C-T is described in ClinVar as [Benign]. Clinvar id is 731726.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00766 (1167/152320) while in subpopulation AFR AF= 0.0265 (1101/41568). AF 95% confidence interval is 0.0252. There are 15 homozygotes in gnomad4. There are 549 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCN2	NM_005564.5	c.371C>T	p.Thr124Met	missense_variant	4/7	ENST00000277480.7	NP_005555.2
LCN2	XM_047423376.1	c.371C>T	p.Thr124Met	missense_variant	4/6		XP_047279332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCN2	ENST00000277480.7	c.371C>T	p.Thr124Met	missense_variant	4/7	1	NM_005564.5	ENSP00000277480	P4

Frequencies

GnomAD3 genomes AF: 0.00761 AC: 1159 AN: 152202 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00212 AC: 534 AN: 251394 Hom.: 7 AF XY: 0.00160 AC XY: 217 AN XY: 135864

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.000926

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000757 AC: 1107 AN: 1461790 Hom.: 17 Cov.: 36 AF XY: 0.000656 AC XY: 477 AN XY: 727198

Gnomad4 AFR exome AF: 0.0258

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000647

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.00766 AC: 1167 AN: 152320 Hom.: 15 Cov.: 33 AF XY: 0.00737 AC XY: 549 AN XY: 74486

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00174 Hom.: 8

Bravo AF: 0.00889

ESP6500AA AF: 0.0254 AC: 112

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00263 AC: 319

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.1
DANN	Benign	0.93
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.63	.;T;T
MetaRNN	Benign	0.0034	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.44	N;N;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.83	N;N;N
REVEL	Benign	0.025
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.085	T;T;T
Polyphen		0.15	B;B;.
Vest4		0.24
MVP		0.061
MPC		0.026
ClinPred		0.00014	T
GERP RS		-3.1
Varity_R		0.044
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs79993583; hg19: chr9-130914200;