17-58244090-GACACACACACACACACACACACAC-GACACACACACACACACAC

Position:

• chr17-58244090-GACACACACACACACACACACACAC-GACACACACACACACACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_006151.3(LPO):​c.164+46_164+51delACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 1,050,386 control chromosomes in the GnomAD database, including 176 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.026 (49 hom., cov: 0)
  • Exomes 𝑓: 0.032 (127 hom.)
• Consequence: LPO NM_006151.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

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

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0264 (3716/140920) while in subpopulation NFE AF= 0.0307 (1991/64910). AF 95% confidence interval is 0.0296. There are 49 homozygotes in gnomad4. There are 1767 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPO	NM_006151.3	c.164+46_164+51delACACAC		intron_variant		ENST00000262290.9	NP_006142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPO	ENST00000262290.9	c.164+46_164+51delACACAC		intron_variant		1	NM_006151.3	ENSP00000262290.4

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 3710 AN: 140820 Hom.: 49 Cov.: 0

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0158

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.0226

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.0127

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.0134

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0246

GnomAD3 exomes AF: 0.0435 AC: 5963 AN: 136960 Hom.: 64 AF XY: 0.0445 AC XY: 3282 AN XY: 73692

Gnomad AFR exome AF: 0.0388

Gnomad AMR exome AF: 0.0191

Gnomad ASJ exome AF: 0.0447

Gnomad EAS exome AF: 0.00838

Gnomad SAS exome AF: 0.0236

Gnomad FIN exome AF: 0.0609

Gnomad NFE exome AF: 0.0632

Gnomad OTH exome AF: 0.0459

GnomAD4 exome AF: 0.0321 AC: 29236 AN: 909466 Hom.: 127 AF XY: 0.0328 AC XY: 15325 AN XY: 467930

Gnomad4 AFR exome AF: 0.0301

Gnomad4 AMR exome AF: 0.0169

Gnomad4 ASJ exome AF: 0.0332

Gnomad4 EAS exome AF: 0.00518

Gnomad4 SAS exome AF: 0.0192

Gnomad4 FIN exome AF: 0.0467

Gnomad4 NFE exome AF: 0.0350

Gnomad4 OTH exome AF: 0.0358

GnomAD4 genome AF: 0.0264 AC: 3716 AN: 140920 Hom.: 49 Cov.: 0 AF XY: 0.0259 AC XY: 1767 AN XY: 68160

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.0221

Gnomad4 ASJ AF: 0.0226

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.0125

Gnomad4 FIN AF: 0.0315

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs67390833; hg19: chr17-56321451;