17-58244090-GACACACACACACACACACACACACACACAC-GACACACACACACACACAC

Variant names:

• chr17-58244090-GACACACACACAC-G
• rs67390833
• NM_006151.3:c.164+40_164+51delACACACACACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006151.3(LPO):​c.164+40_164+51delACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 1,061,232 control chromosomes in the GnomAD database, including 302 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.027 (71 hom., cov: 0)
  • Exomes 𝑓: 0.032 (231 hom.)
• Consequence: LPO NM_006151.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.713
• Publications: 2 publications found

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]

ENSG00000286788 (HGNC:):

ACMG classification

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

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0843 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPO	NM_006151.3	MANE Select	c.164+40_164+51delACACACACACAC		intron	N/A	NP_006142.1
	LPO	NM_001160102.2		c.76+1066_76+1077delACACACACACAC		intron	N/A	NP_001153574.1
	LPO	NR_027647.2		n.234+1066_234+1077delACACACACACAC		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPO	ENST00000262290.9	TSL:1 MANE Select	c.164+40_164+51delACACACACACAC		intron	N/A	ENSP00000262290.4
	LPO	ENST00000421678.6	TSL:1	c.76+1066_76+1077delACACACACACAC		intron	N/A	ENSP00000400245.2
	LPO	ENST00000578403.5	TSL:1	n.235+40_235+51delACACACACACAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 3793 AN: 140866 Hom.: 72 Cov.: 0

Gnomad AFR AF: 0.00638

Gnomad AMI AF: 0.0113

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.0637

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.0556

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0204

GnomAD2 exomes AF: 0.0447 AC: 6121 AN: 136960 AF XY: 0.0486

Gnomad AFR exome AF: 0.00738

Gnomad AMR exome AF: 0.0186

Gnomad ASJ exome AF: 0.0350

Gnomad EAS exome AF: 0.0756

Gnomad FIN exome AF: 0.0646

Gnomad NFE exome AF: 0.0362

Gnomad OTH exome AF: 0.0411

GnomAD4 exome AF: 0.0317 AC: 29184 AN: 920266 Hom.: 231 AF XY: 0.0336 AC XY: 15937 AN XY: 473642

African (AFR) AF: 0.00447 AC: 95 AN: 21268

American (AMR) AF: 0.0147 AC: 575 AN: 39054

Ashkenazi Jewish (ASJ) AF: 0.0275 AC: 607 AN: 22066

East Asian (EAS) AF: 0.0496 AC: 1778 AN: 35848

South Asian (SAS) AF: 0.0764 AC: 5513 AN: 72142

European-Finnish (FIN) AF: 0.0484 AC: 1985 AN: 41012

Middle Eastern (MID) AF: 0.0234 AC: 104 AN: 4442

European-Non Finnish (NFE) AF: 0.0269 AC: 17248 AN: 641944

Other (OTH) AF: 0.0301 AC: 1279 AN: 42490

GnomAD4 genome AF: 0.0269 AC: 3794 AN: 140966 Hom.: 71 Cov.: 0 AF XY: 0.0296 AC XY: 2017 AN XY: 68186

African (AFR) AF: 0.00636 AC: 237 AN: 37248

American (AMR) AF: 0.0169 AC: 239 AN: 14146

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 101 AN: 3362

East Asian (EAS) AF: 0.0638 AC: 302 AN: 4730

South Asian (SAS) AF: 0.0917 AC: 403 AN: 4394

European-Finnish (FIN) AF: 0.0556 AC: 504 AN: 9058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.0302 AC: 1959 AN: 64930

Other (OTH) AF: 0.0202 AC: 39 AN: 1934

Alfa AF: 0.0106 Hom.: 254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs67390833; hg19: chr17-56321451;