Genetic Variant LPO:c.1694-54A>G (chr17-58267295-A-G) – 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.1694-54A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,404,024 control chromosomes in the GnomAD database, including 123,957 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 0.49 ( 20827 hom., cov: 33)

Exomes 𝑓: 0.40 ( 103130 hom. )

Consequence

LPO
NM_006151.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.170

Publications

9 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:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

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.1694-54A>G	intron	N/A	NP_006142.1
LPO	NM_001160102.2		c.1445-54A>G	intron	N/A	NP_001153574.1
LPO	NR_027647.2		n.1764-54A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LPO	ENST00000262290.9	TSL:1 MANE Select	c.1694-54A>G	intron	N/A	ENSP00000262290.4
LPO	ENST00000421678.6	TSL:1	c.1445-54A>G	intron	N/A	ENSP00000400245.2
LPO	ENST00000389576.4	TSL:1	n.*619-54A>G	intron	N/A	ENSP00000374227.4

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74522

AN:

152022

Hom.:

20773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.432

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.453

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.447

GnomAD4 exome

AF:

0.396

AC:

496115

AN:

1251884

Hom.:

103130

AF XY:

0.397

AC XY:

249942

AN XY:

630142

show subpopulations

African (AFR)

AF:

0.797

AC:

23702

AN:

29756

American (AMR)

AF:

0.275

AC:

11861

AN:

43200

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

10909

AN:

23952

East Asian (EAS)

AF:

0.229

AC:

8837

AN:

38562

South Asian (SAS)

AF:

0.434

AC:

34774

AN:

80076

European-Finnish (FIN)

AF:

0.456

AC:

23314

AN:

51088

Middle Eastern (MID)

AF:

0.397

AC:

2126

AN:

5358

European-Non Finnish (NFE)

AF:

0.387

AC:

358880

AN:

926688

Other (OTH)

AF:

0.408

AC:

21712

AN:

53204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

14456

28911

43367

57822

72278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10486

20972

31458

41944

52430

<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:

0.491

AC:

74637

AN:

152140

Hom.:

20827

Cov.:

AF XY:

0.487

AC XY:

36201

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.774

AC:

32144

AN:

41508

American (AMR)

AF:

0.311

AC:

4748

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

1589

AN:

3472

East Asian (EAS)

AF:

0.231

AC:

1193

AN:

5170

South Asian (SAS)

AF:

0.410

AC:

1980

AN:

4824

European-Finnish (FIN)

AF:

0.453

AC:

4786

AN:

10562

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.393

AC:

26742

AN:

68002

Other (OTH)

AF:

0.445

AC:

940

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1781

3562

5343

7124

8905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.410

Hom.:

4812

Bravo

AF:

0.493

Asia WGS

AF:

0.335

AC:

1162

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.0

(source)

DANN

Benign

0.38

PhyloP100

-0.17

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

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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