Genetic Variant LCN6:p.Leu107Ile (chr9-136745263-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_198946.3(LCN6):c.319C>A(p.Leu107Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,612,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L107L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

LCN6
NM_198946.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0690

Publications

4 publications found

Variant links:

Genes affected

LCN6 (HGNC:17337): (lipocalin 6) Predicted to enable small molecule binding activity. Predicted to be involved in single fertilization. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LCN6 links:

ENSG00000204003 (HGNC:):

ENSG00000204003 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073781908).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198946.3. 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
	LCN6	NM_198946.3	MANE Select	c.319C>A	p.Leu107Ile	missense	Exon 4 of 7	NP_945184.1	P62502

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCN6	ENST00000341206.9	TSL:1 MANE Select	c.319C>A	p.Leu107Ile	missense	Exon 4 of 7	ENSP00000339621.3	P62502
LCN6	ENST00000476567.1	TSL:1	c.64C>A	p.Leu22Ile	missense	Exon 2 of 3	ENSP00000468337.1	K7ERN5
ENSG00000204003	ENST00000435202.5	TSL:2	n.289C>A		non_coding_transcript_exon	Exon 4 of 11	ENSP00000399627.1	H7C1C5

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000483

AC:

121

AN:

250742

AF XY:

0.000479

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00319

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000521

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000270

AC:

394

AN:

1460650

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

189

AN XY:

726678

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33468

American (AMR)

AF:

0.000559

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00306

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000174

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52914

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000220

AC:

244

AN:

1111334

Other (OTH)

AF:

0.000381

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

114

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

AF:

0.000223

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41552

American (AMR)

AF:

0.0000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000348

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000889

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.0032

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.50

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0074

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

PhyloP100

0.069

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.83

REVEL

Benign

0.045

Sift

Benign

0.64

Sift4G

Uncertain

0.031

Polyphen

0.13

Vest4

0.22

MVP

0.088

MPC

0.073

ClinPred

0.0090

GERP RS

0.50

Varity_R

0.037

gMVP

0.50

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over