17-58244090-GACACACACACACACACACACACACACACAC-GACACACACACACACACACACACACACACACACAC

Variant names:

• chr17-58244090-G-GACAC
• rs67390833
• NM_006151.3:c.164+48_164+51dupACAC

Variant summary

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

The NM_006151.3(LPO):​c.164+48_164+51dupACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.072 (371 hom., cov: 0)
  • Exomes 𝑓: 0.035 (29 hom.)
• Consequence: LPO NM_006151.3 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.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0808 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPO	NM_006151.3	MANE Select	c.164+48_164+51dupACAC		intron	N/A	NP_006142.1	P22079-1
	LPO	NM_001160102.2		c.76+1074_76+1077dupACAC		intron	N/A	NP_001153574.1	P22079-2
	LPO	NR_027647.2		n.234+1074_234+1077dupACAC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPO	ENST00000262290.9	TSL:1 MANE Select	c.164+48_164+51dupACAC		intron	N/A	ENSP00000262290.4	P22079-1
	LPO	ENST00000421678.6	TSL:1	c.76+1074_76+1077dupACAC		intron	N/A	ENSP00000400245.2	P22079-2
	LPO	ENST00000578403.5	TSL:1	n.235+48_235+51dupACAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10150 AN: 140740 Hom.: 372 Cov.: 0

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.0492

Gnomad FIN AF: 0.0559

Gnomad MID AF: 0.0403

Gnomad NFE AF: 0.0722

Gnomad OTH AF: 0.0643

GnomAD2 exomes AF: 0.0455 AC: 6230 AN: 136960 AF XY: 0.0433

Gnomad AFR exome AF: 0.0551

Gnomad AMR exome AF: 0.0518

Gnomad ASJ exome AF: 0.0242

Gnomad EAS exome AF: 0.0698

Gnomad FIN exome AF: 0.0318

Gnomad NFE exome AF: 0.0446

Gnomad OTH exome AF: 0.0443

GnomAD4 exome AF: 0.0351 AC: 32034 AN: 913648 Hom.: 29 Cov.: 0 AF XY: 0.0358 AC XY: 16820 AN XY: 470158

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

African (AFR) AF: 0.0520 AC: 1089 AN: 20946

American (AMR) AF: 0.0389 AC: 1509 AN: 38764

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 525 AN: 21950

East Asian (EAS) AF: 0.0754 AC: 2669 AN: 35412

South Asian (SAS) AF: 0.0343 AC: 2461 AN: 71712

European-Finnish (FIN) AF: 0.0409 AC: 1663 AN: 40672

Middle Eastern (MID) AF: 0.0249 AC: 110 AN: 4414

European-Non Finnish (NFE) AF: 0.0320 AC: 20393 AN: 637606

Other (OTH) AF: 0.0383 AC: 1615 AN: 42172

⚠️ 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: 0.0721 AC: 10156 AN: 140840 Hom.: 371 Cov.: 0 AF XY: 0.0708 AC XY: 4821 AN XY: 68136

African (AFR) AF: 0.0832 AC: 3096 AN: 37190

American (AMR) AF: 0.0631 AC: 891 AN: 14116

Ashkenazi Jewish (ASJ) AF: 0.0351 AC: 118 AN: 3362

East Asian (EAS) AF: 0.0793 AC: 375 AN: 4730

South Asian (SAS) AF: 0.0498 AC: 219 AN: 4400

European-Finnish (FIN) AF: 0.0559 AC: 506 AN: 9052

Middle Eastern (MID) AF: 0.0435 AC: 12 AN: 276

European-Non Finnish (NFE) AF: 0.0722 AC: 4688 AN: 64892

Other (OTH) AF: 0.0646 AC: 125 AN: 1934

Alfa AF: 0.0480 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;