Variant chr9-135523885-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002297.4(LCN1):c.298G>C(p.Gly100Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00712 in 1,613,578 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 53 hom. )

Consequence

LCN1
NM_002297.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0790

Variant links:

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]

LCN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067055225).

BP6

Variant 9-135523885-G-C is Benign according to our data. Variant chr9-135523885-G-C is described in ClinVar as [Benign]. Clinvar id is 711321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCN1	NM_002297.4 link	c.298G>C	p.Gly100Arg	missense_variant	4/7	ENST00000371781.4	NP_002288.1	P31025A0A024R8D7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCN1	ENST00000371781.4 link	c.298G>C	p.Gly100Arg	missense_variant	4/7	1	NM_002297.4	ENSP00000360846.3		P31025
LCN1	ENST00000263598.6 link	c.298G>C	p.Gly100Arg	missense_variant	4/7	1		ENSP00000263598.2		P31025

Frequencies

GnomAD3 genomes

AF:

0.00529

AC:

805

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00415

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00782

Gnomad OTH

AF:

0.00862

GnomAD3 exomes

AF:

0.00529

AC:

1329

AN:

251336

Hom.:

AF XY:

0.00534

AC XY:

726

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00573

Gnomad ASJ exome

AF:

0.00486

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.00411

Gnomad NFE exome

AF:

0.00794

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

AF:

0.00731

AC:

10676

AN:

1461310

Hom.:

Cov.:

AF XY:

0.00718

AC XY:

5219

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00586

Gnomad4 ASJ exome

AF:

0.00421

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000835

Gnomad4 FIN exome

AF:

0.00389

Gnomad4 NFE exome

AF:

0.00858

Gnomad4 OTH exome

AF:

0.00730

GnomAD4 genome

AF:

0.00529

AC:

805

AN:

152268

Hom.:

Cov.:

AF XY:

0.00522

AC XY:

389

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00415

Gnomad4 NFE

AF:

0.00782

Gnomad4 OTH

AF:

0.00853

Alfa

AF:

0.00694

Hom.:

Bravo

AF:

0.00566

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.00516

AC:

627

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00818

EpiControl

AF:

0.00753

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.60

.;T

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-6.2

D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.29

MVP

0.42

MPC

0.42

ClinPred

0.080

GERP RS

2.1

Varity_R

0.37

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over