rs2232626

Variant names:

• chr9-128151725-T-C
• rs2232626
• NM_005564.5:c.355+8T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005564.5(LCN2):​c.355+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,613,258 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (16 hom.)
• Consequence: LCN2 NM_005564.5 splice_region, intron
• Scores: Splicing: ADA: 0.0002771
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.152
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 9-128151725-T-C is Benign according to our data. Variant chr9-128151725-T-C is described in ClinVar as Benign. ClinVar VariationId is 731724.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00763 (1162/152240) while in subpopulation AFR AF = 0.0265 (1101/41528). AF 95% confidence interval is 0.0252. There are 15 homozygotes in GnomAd4. There are 547 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN2	NM_005564.5	MANE Select	c.355+8T>C		splice_region intron	N/A	NP_005555.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN2	ENST00000277480.7	TSL:1 MANE Select	c.355+8T>C		splice_region intron	N/A	ENSP00000277480.2	P80188-1
	LCN2	ENST00000372998.1	TSL:5	c.361+8T>C		splice_region intron	N/A	ENSP00000362089.1	X6R8F3
	LCN2	ENST00000373017.5	TSL:5	c.355+8T>C		splice_region intron	N/A	ENSP00000362108.1	P80188-1

Frequencies

GnomAD3 genomes AF: 0.00759 AC: 1154 AN: 152122 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

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: 0.0000735

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00210 AC: 528 AN: 251290 AF XY: 0.00155

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000730 AC: 1066 AN: 1461018 Hom.: 16 Cov.: 31 AF XY: 0.000629 AC XY: 457 AN XY: 726778

African (AFR) AF: 0.0258 AC: 865 AN: 33468

American (AMR) AF: 0.00145 AC: 65 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5762

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111278

Other (OTH) AF: 0.00144 AC: 87 AN: 60350

GnomAD4 genome AF: 0.00763 AC: 1162 AN: 152240 Hom.: 15 Cov.: 32 AF XY: 0.00735 AC XY: 547 AN XY: 74446

African (AFR) AF: 0.0265 AC: 1101 AN: 41528

American (AMR) AF: 0.00314 AC: 48 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67990

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00426 Hom.: 7

Bravo AF: 0.00890

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.66
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00028
dbscSNV1_RF	Benign	0.030
SpliceAI score (max)		0.15		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: rs2232626; hg19: chr9-130914004;