dbSNP rs8178290: LPO:c.-2-181C>A (chr17-58242797-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006151.3(LPO):c.-2-181C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 568,408 control chromosomes in the GnomAD database, including 14,592 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4216 hom., cov: 32)

Exomes 𝑓: 0.21 ( 10376 hom. )

Consequence

LPO
NM_006151.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.818

Publications

12 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPO	NM_006151.3 link	c.-2-181C>A		intron_variant	Intron 1 of 12	ENST00000262290.9	NP_006142.1	P22079-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPO	ENST00000262290.9 link	c.-2-181C>A		intron_variant	Intron 1 of 12	1	NM_006151.3	ENSP00000262290.4		P22079-1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35110

AN:

151956

Hom.:

4206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.195

GnomAD4 exome

AF:

0.214

AC:

89210

AN:

416334

Hom.:

10376

AF XY:

0.214

AC XY:

47107

AN XY:

220292

show subpopulations

African (AFR)

AF:

0.271

AC:

3069

AN:

11324

American (AMR)

AF:

0.143

AC:

2389

AN:

16692

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

2226

AN:

12486

East Asian (EAS)

AF:

0.126

AC:

3508

AN:

27924

South Asian (SAS)

AF:

0.227

AC:

9513

AN:

41978

European-Finnish (FIN)

AF:

0.311

AC:

9074

AN:

29146

Middle Eastern (MID)

AF:

0.126

AC:

372

AN:

2960

European-Non Finnish (NFE)

AF:

0.217

AC:

54206

AN:

249864

Other (OTH)

AF:

0.203

AC:

4853

AN:

23960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

3115

6229

9344

12458

15573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.231

AC:

35156

AN:

152074

Hom.:

4216

Cov.:

AF XY:

0.233

AC XY:

17354

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.277

AC:

11479

AN:

41476

American (AMR)

AF:

0.149

AC:

2282

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

601

AN:

3470

East Asian (EAS)

AF:

0.127

AC:

659

AN:

5180

South Asian (SAS)

AF:

0.218

AC:

1051

AN:

4822

European-Finnish (FIN)

AF:

0.325

AC:

3431

AN:

10564

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.220

AC:

14983

AN:

67954

Other (OTH)

AF:

0.196

AC:

413

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1366

2732

4098

5464

6830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.209

Hom.:

4453

Bravo

AF:

0.218

Asia WGS

AF:

0.169

AC:

587

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.0

(source)

DANN

Benign

0.49

PhyloP100

0.82

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over