17-58244090-GACACACACACACACACACACACACACACAC-GACACACACACACACACACACACACACACACAC

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000262290.9(LPO):​c.164+50_164+51dupAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1245 hom., cov: 0)
  • Exomes 𝑓: 0.049 (31 hom.)
• Consequence: LPO ENST00000262290.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 17-58244090-G-GAC is Benign according to our data. Variant chr17-58244090-G-GAC is described in ClinVar as Benign. ClinVar VariationId is 403046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

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+50_164+51dupAC		intron	N/A	NP_006142.1
	LPO	NM_001160102.2		c.76+1076_76+1077dupAC		intron	N/A	NP_001153574.1
	LPO	NR_027647.2		n.234+1076_234+1077dupAC		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+51dupAC		intron	N/A	ENSP00000262290.4
	LPO	ENST00000421678.6	TSL:1	c.76+1076_76+1077dupAC		intron	N/A	ENSP00000400245.2
	LPO	ENST00000578403.5	TSL:1	n.235+50_235+51dupAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.119 AC: 16715 AN: 140600 Hom.: 1239 Cov.: 0

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.0440

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0763

Gnomad OTH AF: 0.110

GnomAD2 exomes AF: 0.0664 AC: 9099 AN: 136960 AF XY: 0.0644

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.0623

Gnomad ASJ exome AF: 0.0346

Gnomad EAS exome AF: 0.0804

Gnomad FIN exome AF: 0.0598

Gnomad NFE exome AF: 0.0537

Gnomad OTH exome AF: 0.0679

GnomAD4 exome AF: 0.0487 AC: 44364 AN: 911362 Hom.: 31 Cov.: 0 AF XY: 0.0499 AC XY: 23427 AN XY: 469016

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

African (AFR) AF: 0.138 AC: 2864 AN: 20718

American (AMR) AF: 0.0494 AC: 1908 AN: 38596

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 756 AN: 21838

East Asian (EAS) AF: 0.0783 AC: 2766 AN: 35340

South Asian (SAS) AF: 0.0759 AC: 5393 AN: 71044

European-Finnish (FIN) AF: 0.0781 AC: 3164 AN: 40500

Middle Eastern (MID) AF: 0.0589 AC: 259 AN: 4400

European-Non Finnish (NFE) AF: 0.0389 AC: 24786 AN: 636884

Other (OTH) AF: 0.0587 AC: 2468 AN: 42042

⚠️ 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: 0.119 AC: 16753 AN: 140700 Hom.: 1245 Cov.: 0 AF XY: 0.119 AC XY: 8067 AN XY: 68054

African (AFR) AF: 0.226 AC: 8367 AN: 37096

American (AMR) AF: 0.0849 AC: 1199 AN: 14120

Ashkenazi Jewish (ASJ) AF: 0.0440 AC: 148 AN: 3360

East Asian (EAS) AF: 0.0843 AC: 399 AN: 4732

South Asian (SAS) AF: 0.104 AC: 457 AN: 4390

European-Finnish (FIN) AF: 0.0935 AC: 845 AN: 9042

Middle Eastern (MID) AF: 0.120 AC: 33 AN: 276

European-Non Finnish (NFE) AF: 0.0763 AC: 4948 AN: 64870

Other (OTH) AF: 0.112 AC: 216 AN: 1926

Alfa AF: 0.0617 Hom.: 254

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

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;