rs377244175

Variant names:

• chr9-135524880-G-A
• rs377244175
• NM_002297.4:c.454G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-135524880-G-A
• chr9-135524880-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002297.4(LCN1):​c.454G>A​(p.Ala152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,607,932 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: LCN1 NM_002297.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.598
• Publications: 1 publications found

Genes affected

LCN1 (HGNC:6525): (lipocalin 1) This gene encodes a member of the lipocalin family of small secretory proteins. Lipocalins are extracellular transport proteins that bind to a variety of hydrophobic ligands. The encoded protein is the primary lipid binding protein in tears and is overproduced in response to multiple stimuli including infection and stress. The encoded protein may be a marker for chromosome aneuploidy as well as an autoantigen in Sjogren's syndrome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and two pseudogenes of this gene are also located on the long arm of chromosome 9. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.097061485).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002297.4. 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
	LCN1	NM_002297.4	MANE Select	c.454G>A	p.Ala152Thr	missense	Exon 5 of 7	NP_002288.1	P31025
	LCN1	NM_001252617.2		c.454G>A	p.Ala152Thr	missense	Exon 5 of 7	NP_001239546.1	P31025
	LCN1	NM_001252618.2		c.450G>A	p.Pro150Pro	synonymous	Exon 5 of 7	NP_001239547.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN1	ENST00000371781.4	TSL:1 MANE Select	c.454G>A	p.Ala152Thr	missense	Exon 5 of 7	ENSP00000360846.3	P31025
	LCN1	ENST00000263598.6	TSL:1	c.454G>A	p.Ala152Thr	missense	Exon 5 of 7	ENSP00000263598.2	P31025

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000419 AC: 10 AN: 238422 AF XY: 0.0000232

Gnomad AFR exome AF: 0.000200

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000187

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1455770 Hom.: 0 Cov.: 31 AF XY: 0.00000691 AC XY: 5 AN XY: 723718

African (AFR) AF: 0.0000902 AC: 3 AN: 33248

American (AMR) AF: 0.0000681 AC: 3 AN: 44084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39248

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00000631 AC: 7 AN: 1109374

Other (OTH) AF: 0.00 AC: 0 AN: 60088

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74332

African (AFR) AF: 0.0000724 AC: 3 AN: 41438

American (AMR) AF: 0.000393 AC: 6 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000682 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.40
DANN	Benign	0.95
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.60
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.15
Sift	Benign	0.25	T
Sift4G	Benign	0.33	T
Polyphen		0.98	D
Vest4		0.18
MVP		0.21
MPC		0.15
ClinPred		0.072	T
GERP RS		-6.6
Varity_R		0.084
gMVP		0.27
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs377244175; hg19: chr9-138416726;