NM_002297.4:c.184C>T

Variant names:

• chr9-135522140-C-T
• rs764304003
• NM_002297.4:c.184C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002297.4(LCN1):​c.184C>T​(p.Leu62Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,450,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LCN1 NM_002297.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.75 with no splicing effect.

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.184C>T	p.Leu62Leu	synonymous	Exon 2 of 7	NP_002288.1	P31025
	LCN1	NM_001252618.2		c.184C>T	p.Leu62Leu	synonymous	Exon 2 of 7	NP_001239547.1
	LCN1	NM_001252619.2		c.184C>T	p.Leu62Leu	synonymous	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.184C>T	p.Leu62Leu	synonymous	Exon 2 of 7	ENSP00000360846.3	P31025
	LCN1	ENST00000263598.6	TSL:1	c.184C>T	p.Leu62Leu	synonymous	Exon 2 of 7	ENSP00000263598.2	P31025

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1450256 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 720614

African (AFR) AF: 0.00 AC: 0 AN: 33086

American (AMR) AF: 0.0000232 AC: 1 AN: 43136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25862

East Asian (EAS) AF: 0.00 AC: 0 AN: 38992

South Asian (SAS) AF: 0.00 AC: 0 AN: 84444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106650

Other (OTH) AF: 0.00 AC: 0 AN: 59846

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.73
DANN	Benign	0.62
PhyloP100		0.75

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: rs764304003; hg19: chr9-138413986;