rs8178409

Positions:

• chr17-58267506-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006151.3(LPO):​c.1851G>A​(p.Pro617=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,614,012 control chromosomes in the GnomAD database, including 34,444 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3042 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31402 hom.)
• Consequence: LPO NM_006151.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPO	NM_006151.3	c.1851G>A	p.Pro617=	synonymous_variant	12/13	ENST00000262290.9	NP_006142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPO	ENST00000262290.9	c.1851G>A	p.Pro617=	synonymous_variant	12/13	1	NM_006151.3	ENSP00000262290	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29868 AN: 152082 Hom.: 3030 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.177

GnomAD3 exomes AF: 0.198 AC: 49712 AN: 251322 Hom.: 5293 AF XY: 0.200 AC XY: 27133 AN XY: 135854

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.130

Gnomad SAS exome AF: 0.216

Gnomad FIN exome AF: 0.278

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.204 AC: 297522 AN: 1461812 Hom.: 31402 Cov.: 33 AF XY: 0.203 AC XY: 147862 AN XY: 727218

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.197 AC: 29910 AN: 152200 Hom.: 3042 Cov.: 32 AF XY: 0.197 AC XY: 14648 AN XY: 74404

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.178

Alfa AF: 0.202 Hom.: 1935

Bravo AF: 0.185

Asia WGS AF: 0.165 AC: 570 AN: 3478

EpiCase AF: 0.186

EpiControl AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8178409; hg19: chr17-56344867; COSMIC: COSV51857271; COSMIC: COSV51857271;