Genetic Variant LPO:c.164+46_164+51dupACACAC (chr17-58244090-G-GACACAC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_006151.3(LPO):c.164+46_164+51dupACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.021 ( 44 hom., cov: 0)

Exomes 𝑓: 0.0095 ( 11 hom. )

Consequence

LPO
NM_006151.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.134

Publications

2 publications found

Variant links:

Genes affected

LPO (HGNC:6678): (lactoperoxidase) This gene encodes a member of the peroxidase family of proteins. The encoded preproprotein is proteolytically processed to generate the mature enzyme. Following its secretion from salivary, mammary, and other mucosal glands, this enzyme catalyzes the generation of the antimicrobial substance hypothiocyanous acid. This gene is present in a gene cluster on chromosome 17. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

LPO links:

ENSG00000286788 (HGNC:):

ENSG00000286788 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0211 (2967/140922) while in subpopulation AFR AF = 0.02 (743/37232). AF 95% confidence interval is 0.0188. There are 44 homozygotes in GnomAd4. There are 1541 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006151.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LPO	NM_006151.3	MANE Select	c.164+46_164+51dupACACAC	intron	N/A	NP_006142.1
LPO	NM_001160102.2		c.76+1072_76+1077dupACACAC	intron	N/A	NP_001153574.1
LPO	NR_027647.2		n.234+1072_234+1077dupACACAC	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LPO	ENST00000262290.9	TSL:1 MANE Select	c.164+46_164+51dupACACAC	intron	N/A	ENSP00000262290.4
LPO	ENST00000421678.6	TSL:1	c.76+1072_76+1077dupACACAC	intron	N/A	ENSP00000400245.2
LPO	ENST00000578403.5	TSL:1	n.235+46_235+51dupACACAC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

2962

AN:

140822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.00208

Gnomad EAS

AF:

0.00612

Gnomad SAS

AF:

0.00817

Gnomad FIN

AF:

0.0665

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.0162

GnomAD4 exome

AF:

0.00947

AC:

8697

AN:

918194

Hom.:

Cov.:

AF XY:

0.00932

AC XY:

4403

AN XY:

472546

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0127

AC:

269

AN:

21186

American (AMR)

AF:

0.0115

AC:

448

AN:

38958

Ashkenazi Jewish (ASJ)

AF:

0.00168

AC:

AN:

22048

East Asian (EAS)

AF:

0.00464

AC:

166

AN:

35806

South Asian (SAS)

AF:

0.00462

AC:

333

AN:

72108

European-Finnish (FIN)

AF:

0.0434

AC:

1759

AN:

40574

Middle Eastern (MID)

AF:

0.00361

AC:

AN:

4436

European-Non Finnish (NFE)

AF:

0.00814

AC:

5213

AN:

640678

Other (OTH)

AF:

0.0108

AC:

456

AN:

42400

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.356

Heterozygous variant carriers

444

889

1333

1778

2222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.0211

AC:

2967

AN:

140922

Hom.:

Cov.:

AF XY:

0.0226

AC XY:

1541

AN XY:

68172

show subpopulations

African (AFR)

AF:

0.0200

AC:

743

AN:

37232

American (AMR)

AF:

0.0168

AC:

237

AN:

14144

Ashkenazi Jewish (ASJ)

AF:

0.00208

AC:

AN:

3358

East Asian (EAS)

AF:

0.00655

AC:

AN:

4732

South Asian (SAS)

AF:

0.00819

AC:

AN:

4396

European-Finnish (FIN)

AF:

0.0665

AC:

602

AN:

9048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.0197

AC:

1280

AN:

64914

Other (OTH)

AF:

0.0160

AC:

AN:

1934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

119

238

356

475

594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0123

Hom.:

254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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