NM_006151.3:c.164+50_164+51delAC

Variant names:

• chr17-58244090-GAC-G
• rs67390833
• NM_006151.3:c.164+50_164+51delAC

Variant summary

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

The NM_006151.3(LPO):​c.164+50_164+51delAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.08 in 1,036,622 control chromosomes in the GnomAD database, including 649 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.081 (481 hom., cov: 0)
  • Exomes 𝑓: 0.080 (168 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 = 0.107 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+50_164+51delAC		intron	N/A	NP_006142.1
	LPO	NM_001160102.2		c.76+1076_76+1077delAC		intron	N/A	NP_001153574.1
	LPO	NR_027647.2		n.234+1076_234+1077delAC		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+50_164+51delAC		intron	N/A	ENSP00000262290.4
	LPO	ENST00000421678.6	TSL:1	c.76+1076_76+1077delAC		intron	N/A	ENSP00000400245.2
	LPO	ENST00000578403.5	TSL:1	n.235+50_235+51delAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 11430 AN: 140690 Hom.: 480 Cov.: 0

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0968

Gnomad AMR AF: 0.0704

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.0720

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.0451

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.0891

GnomAD2 exomes AF: 0.110 AC: 15071 AN: 136960 AF XY: 0.111

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.119

Gnomad EAS exome AF: 0.154

Gnomad FIN exome AF: 0.0741

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.0798 AC: 71447 AN: 895836 Hom.: 168 AF XY: 0.0823 AC XY: 37902 AN XY: 460642

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

African (AFR) AF: 0.0887 AC: 1861 AN: 20990

American (AMR) AF: 0.0931 AC: 3497 AN: 37554

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 2648 AN: 21226

East Asian (EAS) AF: 0.165 AC: 5454 AN: 33036

South Asian (SAS) AF: 0.108 AC: 7509 AN: 69480

European-Finnish (FIN) AF: 0.0783 AC: 3098 AN: 39542

Middle Eastern (MID) AF: 0.138 AC: 596 AN: 4322

European-Non Finnish (NFE) AF: 0.0683 AC: 42931 AN: 628484

Other (OTH) AF: 0.0935 AC: 3853 AN: 41202

⚠️ 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: 0.0813 AC: 11442 AN: 140786 Hom.: 481 Cov.: 0 AF XY: 0.0797 AC XY: 5428 AN XY: 68108

African (AFR) AF: 0.110 AC: 4098 AN: 37204

American (AMR) AF: 0.0703 AC: 992 AN: 14120

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 330 AN: 3358

East Asian (EAS) AF: 0.0720 AC: 340 AN: 4724

South Asian (SAS) AF: 0.0847 AC: 372 AN: 4394

European-Finnish (FIN) AF: 0.0451 AC: 407 AN: 9024

Middle Eastern (MID) AF: 0.123 AC: 34 AN: 276

European-Non Finnish (NFE) AF: 0.0711 AC: 4612 AN: 64870

Other (OTH) AF: 0.0887 AC: 171 AN: 1928

Alfa AF: 0.0881 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

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs67390833; hg19: chr17-56321451;