chr17-58244090-GACACACACACACACACACACACACACACAC-G

Variant names:

• chr17-58244090-GACACACACACACACACACACACACACACAC-G
• rs67390833
• NM_006151.3:c.164+22_164+51delACACACACACACACACACACACACACACAC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006151.3(LPO):​c.164+22_164+51delACACACACACACACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000543 in 920,436 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: LPO NM_006151.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.713
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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+22_164+51delACACACACACACACACACACACACACACAC		intron	N/A	NP_006142.1
	LPO	NM_001160102.2		c.76+1048_76+1077delACACACACACACACACACACACACACACAC		intron	N/A	NP_001153574.1
	LPO	NR_027647.2		n.234+1048_234+1077delACACACACACACACACACACACACACACAC		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+22_164+51delACACACACACACACACACACACACACACAC		intron	N/A	ENSP00000262290.4
	LPO	ENST00000421678.6	TSL:1	c.76+1048_76+1077delACACACACACACACACACACACACACACAC		intron	N/A	ENSP00000400245.2
	LPO	ENST00000578403.5	TSL:1	n.235+22_235+51delACACACACACACACACACACACACACACAC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000543 AC: 5 AN: 920436 Hom.: 0 AF XY: 0.00000211 AC XY: 1 AN XY: 473738

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

African (AFR) AF: 0.00 AC: 0 AN: 21272

American (AMR) AF: 0.00 AC: 0 AN: 39060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22068

East Asian (EAS) AF: 0.00 AC: 0 AN: 35860

South Asian (SAS) AF: 0.00 AC: 0 AN: 72206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4446

European-Non Finnish (NFE) AF: 0.00000779 AC: 5 AN: 641994

Other (OTH) AF: 0.00 AC: 0 AN: 42508

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.71

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;