17-58244090-GACACACACACACACACACACACACACACAC-GACACACACACACACACACACACAC

Variant names:

• chr17-58244090-GACACAC-G
• rs67390833
• NM_006151.3:c.164+46_164+51delACACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000262290.9(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 ENST00000262290.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• 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.

• 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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 49 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262290.9. 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+46_164+51delACACAC		intron	N/A	NP_006142.1
	LPO	NM_001160102.2		c.76+1072_76+1077delACACAC		intron	N/A	NP_001153574.1
	LPO	NR_027647.2		n.234+1072_234+1077delACACAC		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+46_164+51delACACAC		intron	N/A	ENSP00000262290.4
	LPO	ENST00000421678.6	TSL:1	c.76+1072_76+1077delACACAC		intron	N/A	ENSP00000400245.2
	LPO	ENST00000578403.5	TSL:1	n.235+46_235+51delACACAC		intron	N/A

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

GnomAD2 exomes AF: 0.0435 AC: 5963 AN: 136960 AF XY: 0.0445

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 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

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

African (AFR) AF: 0.0301 AC: 635 AN: 21126

American (AMR) AF: 0.0169 AC: 656 AN: 38780

Ashkenazi Jewish (ASJ) AF: 0.0332 AC: 723 AN: 21760

East Asian (EAS) AF: 0.00518 AC: 185 AN: 35702

South Asian (SAS) AF: 0.0192 AC: 1372 AN: 71592

European-Finnish (FIN) AF: 0.0467 AC: 1872 AN: 40102

Middle Eastern (MID) AF: 0.0287 AC: 126 AN: 4394

European-Non Finnish (NFE) AF: 0.0350 AC: 22168 AN: 634120

Other (OTH) AF: 0.0358 AC: 1499 AN: 41890

⚠️ 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.

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

African (AFR) AF: 0.0245 AC: 911 AN: 37244

American (AMR) AF: 0.0221 AC: 313 AN: 14136

Ashkenazi Jewish (ASJ) AF: 0.0226 AC: 76 AN: 3360

East Asian (EAS) AF: 0.00444 AC: 21 AN: 4730

South Asian (SAS) AF: 0.0125 AC: 55 AN: 4396

European-Finnish (FIN) AF: 0.0315 AC: 285 AN: 9046

Middle Eastern (MID) AF: 0.0145 AC: 4 AN: 276

European-Non Finnish (NFE) AF: 0.0307 AC: 1991 AN: 64910

Other (OTH) AF: 0.0238 AC: 46 AN: 1934

Alfa AF: 0.0306 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 (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;