rs201351780

Variant names:

• chr9-135522114-C-T
• rs201351780
• NM_002297.4:c.158C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002297.4(LCN1):​c.158C>T​(p.Ser53Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,597,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: LCN1 NM_002297.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.989
• Publications: 0 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012642592).

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.158C>T	p.Ser53Leu	missense	Exon 2 of 7	NP_002288.1	P31025
	LCN1	NM_001252618.2		c.158C>T	p.Ser53Leu	missense	Exon 2 of 7	NP_001239547.1
	LCN1	NM_001252619.2		c.158C>T	p.Ser53Leu	missense	Exon 2 of 7	NP_001239548.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN1	ENST00000371781.4	TSL:1 MANE Select	c.158C>T	p.Ser53Leu	missense	Exon 2 of 7	ENSP00000360846.3	P31025
	LCN1	ENST00000263598.6	TSL:1	c.158C>T	p.Ser53Leu	missense	Exon 2 of 7	ENSP00000263598.2	P31025

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152114 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000767 AC: 14 AN: 182534 AF XY: 0.0000820

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000988

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000194 AC: 28 AN: 1445410 Hom.: 0 Cov.: 32 AF XY: 0.0000181 AC XY: 13 AN XY: 717726

African (AFR) AF: 0.00 AC: 0 AN: 33012

American (AMR) AF: 0.00 AC: 0 AN: 42114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25764

East Asian (EAS) AF: 0.000568 AC: 22 AN: 38744

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5572

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1104358

Other (OTH) AF: 0.0000503 AC: 3 AN: 59670

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152232 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74430

African (AFR) AF: 0.00 AC: 0 AN: 41534

American (AMR) AF: 0.00 AC: 0 AN: 15300

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

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000499 AC: 6

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	0.11
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.84
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.99
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.027
Sift	Benign	0.18	T
Sift4G	Benign	0.20	T
Polyphen		0.78	P
Vest4		0.14
MVP		0.15
MPC		0.26
ClinPred		0.068	T
GERP RS		-3.2
Varity_R		0.094
gMVP		0.54
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: rs201351780; hg19: chr9-138413960;