9-135522143-G-A

Variant names:

• chr9-135522143-G-A
• rs1564228549
• NM_002297.4:c.187G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002297.4(LCN1):​c.187G>A​(p.Glu63Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LCN1 NM_002297.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16146088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCN1	NM_002297.4	c.187G>A	p.Glu63Lys	missense_variant	Exon 2 of 7	ENST00000371781.4	NP_002288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCN1	ENST00000371781.4	c.187G>A	p.Glu63Lys	missense_variant	Exon 2 of 7	1	NM_002297.4	ENSP00000360846.3
LCN1	ENST00000263598.6	c.187G>A	p.Glu63Lys	missense_variant	Exon 2 of 7	1		ENSP00000263598.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000469 AC: 1 AN: 213380 Hom.: 0 AF XY: 0.00000866 AC XY: 1 AN XY: 115434

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1451098 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 721082

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.75	.;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.045
Sift	Benign	0.10	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.52	P;P
Vest4		0.15
MutPred		0.52		Gain of ubiquitination at E63 (P = 0.0185);Gain of ubiquitination at E63 (P = 0.0185);
MVP		0.40
MPC		0.33
ClinPred		0.52	D
GERP RS		1.9
Varity_R		0.32
gMVP		0.48

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: rs1564228549; hg19: chr9-138413989;