dbSNP rs150773074: LCN8:p.Arg119Pro (chr9-136755309-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178469.4(LCN8):c.356G>C(p.Arg119Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,098 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R119W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

LCN8
NM_178469.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.89

Publications

6 publications found

Variant links:

Genes affected

LCN8 (HGNC:27038): (lipocalin 8) Members of the lipocalin family, such as LCN8, have a common structure consisting of an 8-stranded antiparallel beta-barrel that forms a cup-shaped ligand-binding pocket or calyx. Lipocalins generally bind small hydrophobic ligands and transport them to specific cells (Suzuki et al., 2004 [PubMed 15363845]).[supplied by OMIM, Aug 2009]

LCN8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11201814).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178469.4. 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
	LCN8	NM_178469.4	MANE Select	c.356G>C	p.Arg119Pro	missense	Exon 5 of 7	NP_848564.2
	LCN8	NM_001345934.2		c.425G>C	p.Arg142Pro	missense	Exon 5 of 7	NP_001332863.1	Q6JVE9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCN8	ENST00000371688.8	TSL:1 MANE Select	c.356G>C	p.Arg119Pro	missense	Exon 5 of 7	ENSP00000360753.3	Q6JVE9-2
LCN8	ENST00000612714.1	TSL:1	c.425G>C	p.Arg142Pro	missense	Exon 5 of 7	ENSP00000482512.1	Q6JVE9-1
LCN8	ENST00000479767.1	TSL:1	n.754G>C		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458098

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725612

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111966

Other (OTH)

AF:

0.00

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.0060

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.0016

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.38

M_CAP

Benign

0.0023

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

PhyloP100

-3.9

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.31

REVEL

Benign

0.016

Sift

Uncertain

0.022

Sift4G

Benign

0.12

Polyphen

0.41

Vest4

0.25

MutPred

0.52

Loss of MoRF binding (P = 0.001)

MVP

0.11

MPC

0.30

ClinPred

0.19

GERP RS

-4.7

Varity_R

0.13

gMVP

0.80

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over